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Ivonescimab (依达方®) is a first-in-class, humanized, tetravalent bispecific monoclonal antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF)-A being developed by Akeso Biopharma for the treatment of non-small cell lung cancer (NSCLC) and other solid tumours, including breast cancer, liver cancer and gastric cancer. Ivonescimab simultaneously blocks the binding of PD-1 to its ligand (PD-L1), thereby relieving PD-1/PD-L1-mediated immunosuppression, and blocks the binding of VEGF-A to its receptor (VEGFR2), thus blocking tumour angiogenesis in the tumour microenvironment. In May 2024, ivonescimab, in combination with pemetrexed and carboplatin, received its first approval in China for the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed after tyrosine kinase inhibitor (TKI) therapy. Clinical studies of ivonescimab are underway in multiple countries worldwide. This article summarizes the milestones in the development of ivonescimab leading to this first approval for EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed after TKI therapy. [ABSTRACT FROM AUTHOR]

Objectives There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. Methods We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001–2021 to investigate the incidence and outcomes related to renal relapse. Results Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [ n  = 36 (38%)] or MMF [ n  = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [ n  = 53 (54%)] or AZA [ n  = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s. d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P  = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P  = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P  = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P  = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3–5) and end-stage kidney disease (17.9% vs 1.8%, P  < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P  = 0.02), osteopenia (38.5% vs 17.9%, P  = 0.04) and hypertension (30.8% vs 7.1%, P  < 0.01). Conclusion Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse. [ABSTRACT FROM AUTHOR]

To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural–urban communities of Southwestern China. Retrospective cohort study. Data on HIV/AIDS cases reported in 2005–20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural–urban regions were compared using Kaplan–Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28–1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29–1.55; p < 0.0001), AHD cohort (1.38, 1.24–1.54; p < 0.0001), and SIS cohort (1.49, 1.23–1.81; p < 0.0001). A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk. [ABSTRACT FROM AUTHOR]

Introduction: Human brucellosis, a Brucella infection caused most common zoonosis in the world, remains a serious public health burden in China. Brucella chronic infection always causes immunosuppressive status and results in severe organ or tissue damages. The aim of this work was to study the role of the myeloid-derived suppressor cells (MDSCs) in human chronic brucellosis. Methods: Fifty cases of chronic brucellosis and 40 healthy individual controls were enrolled in this study. We analyzed the frequency and subsets of MDSCs in PBMC between the chronic brucellosis and healthy control groups by flow cytometry. Furthermore, we also measured the inflammatory-related cytokines in serum samples and the MDSCs inhibition ability to the proliferation of T cells in vitro. Results: We found that the frequency of MDSCs in peripheral blood and the level of IL-6 and IL-10 Th2 cytokines and Arginase-1 were significantly increased in chronic brucellosis patients. In addition, we also found that the T cell function was suppressed in vitro by co-culturing with MDSCs from brucellosis patients. Conclusion: Our study described an increase of immunosuppressive MDSCs in peripheral blood of chronic brucellosis patients. These results contribute to the understanding of Brucella persistent infection, which may provide an insight for effective treatment of chronic brucellosis patients in clinical practice. [ABSTRACT FROM AUTHOR]

Bursa of Fabricius (BOF) is a unique immune organ of birds. It is the place where lymphocytes develop, differentiate and mature. Young chicken BOF is susceptible to infection and damage, and even atrophy, causing immune suppression, and bringing huge economic losses to chicken production. Therefore, studying the regulatory mechanism of chicken bursa development is of great practical significance for disease prevention and diagnosis. Jinhu silky chicken (JSC) is a local excellent breed in the Fujian Province of China and with strong disease resistance. However, studies on the disease resistance of JSC are scarce. This study aimed to provide a theoretical basis for reproduction and disease control of JSC. Developmental features of the structure and the IL‐21‐positive cell (IL‐21 PC) distribution on the BOF in JSC were measured from 7 to 300 days of age. Bursas of chicken (n = 36) were taken at 7, 35, 70, 150, 240, and 300 days of age for preparation of paraffin sections and stained with hematoxylin–eosin (HE) and immunohistochemistry. The microstructure of JSC's BOF was similar to that of other poultry. The cortical‐medullary boundary of the bursa nodule was not obvious at 7 days of age, but it was evident after 35 days of age. Before 70 days of age, IL‐21 positive cells (PC) were scattered on the BOF. At 150 days of age, the number of IL‐21 PC in the bursa were the highest and the nuclei were clear. The level of IL‐21 PC gradually decreased with age. The BOF degenerated and disappeared in 300‐day‐old JSC. The histological structure of the BOF was similar to that of other poultry. IL‐21 PC were widespread in the BOF at different ages, but the numbers were different. Research Highlights: Young chicken bursa of Fabricius (BOF) is susceptible to infection bringing huge economic losses to chicken production.Jinhu silky chicken (JSC) is a local excellent breed of China, but there are limited studies on the disease resistance of JSC.Developmental features and the IL‐21 positive cell distribution on the BOF in JSC were measured from 7 to 300 days of age.This study provided a theoretical basis for reproduction and disease control of JSC. [ABSTRACT FROM AUTHOR]

Microplastic pollution is becoming a major issue for human health due to the recent discovery of microplastics in most ecosystems. Here, we review the sources, formation, occurrence, toxicity and remediation methods of microplastics. We distinguish ocean-based and land-based sources of microplastics. Microplastics have been found in biological samples such as faeces, sputum, saliva, blood and placenta. Cancer, intestinal, pulmonary, cardiovascular, infectious and inflammatory diseases are induced or mediated by microplastics. Microplastic exposure during pregnancy and maternal period is also discussed. Remediation methods include coagulation, membrane bioreactors, sand filtration, adsorption, photocatalytic degradation, electrocoagulation and magnetic separation. Control strategies comprise reducing plastic usage, behavioural change, and using biodegradable plastics. Global plastic production has risen dramatically over the past 70 years to reach 359 million tonnes. China is the world's top producer, contributing 17.5% to global production, while Turkey generates the most plastic waste in the Mediterranean region, at 144 tonnes per day. Microplastics comprise 75% of marine waste, with land-based sources responsible for 80–90% of pollution, while ocean-based sources account for only 10–20%. Microplastics induce toxic effects on humans and animals, such as cytotoxicity, immune response, oxidative stress, barrier attributes, and genotoxicity, even at minimal dosages of 10 μg/mL. Ingestion of microplastics by marine animals results in alterations in gastrointestinal tract physiology, immune system depression, oxidative stress, cytotoxicity, differential gene expression, and growth inhibition. Furthermore, bioaccumulation of microplastics in the tissues of aquatic organisms can have adverse effects on the aquatic ecosystem, with potential transmission of microplastics to humans and birds. Changing individual behaviours and governmental actions, such as implementing bans, taxes, or pricing on plastic carrier bags, has significantly reduced plastic consumption to 8–85% in various countries worldwide. The microplastic minimisation approach follows an upside-down pyramid, starting with prevention, followed by reducing, reusing, recycling, recovering, and ending with disposal as the least preferable option. [ABSTRACT FROM AUTHOR]

Despite highly effective vaccines, Marek's disease (MD) causes great economic loss to the poultry industry annually, largely due to the continuous emergence of new MD virus (MDV) strains. To explore the pathogenic characteristics of newly emerged MDV strains, we selected two strains (AH/1807 and DH/18) with clinically different pathotypes. We studied each strain's infection process and pathogenicity and observed differences in immunosuppression and vaccine resistance. Specific pathogen-free chickens, unvaccinated or vaccinated with CVI988, were challenged with AH/1807 or DH/18. Both infections induced MD damage; however, differences were observed in terms of mortality (AH/1807: 77.8%, DH/18: 50%) and tumor rates (AH/1807: 50%, DH/18: 33.3%). The immune protection indices of the vaccine also differed (AH/1807: 94.1, DH/18: 61.1). Additionally, while both strains caused interferon-β and interferon-γ expression to decline, DH/18 infection caused stronger immunosuppression than AH/1807. This inhibition persisted even after vaccination, leading to increased replication of DH/18 that ultimately broke through vaccine immune protection. These results indicate that both strains have different characteristics, and that strains such as DH/18, which cause weaker pathogenic damage but can break through vaccine immune protection, require further attention. Our findings increase the understanding of the differences between epidemic strains and factors underlying MD vaccination failure in China. [ABSTRACT FROM AUTHOR]

Background: Patients with work-related lung disease (WRLD) are at increased risk of death caused by severe lung tissue damage and fibrosis. This study aimed to assess the clinical outcomes of lung transplantation (LTx) for WRLD and compare the results of LTx between WRLD and idiopathic pulmonary fibrosis (IPF). Methods: This single-center retrospective cohort study reviewed the clinical data of patients who underwent LTx for WRLD or IPF at our hospital between January 2015 and December 2021. Cumulative survival rates after LTx were estimated using the Kaplan-Meier method. Results: The final analysis included 33 cases of WRLD and 91 cases of IPF. The 33 WRLD patients consisted of 19 (57.6%) cases of silicosis, 8 (24.2%) cases of coal workers' pneumoconiosis, 3 (9.09%) cases of asbestosis, and 3 (9.09%) cases of other WRLD. Pneumothorax as an indication for LTx was significantly more common in the WRLD group than in the IPF group (51.5% vs. 2.2%, P < 0.001). There was no significant difference in the 5-year cumulative survival rate between the WRLD patients and the IPF patients (66.6% vs. 56.7%, P = 0.67). There was no significant difference in the best performance of exercise capacity and lung function between the two groups at 1 year post-transplant. Conclusions: LTx had similar survival outcomes and lung function for WRLD and IPF patients. Pneumothorax was the primary indication for lung transplantation in WRLD. [ABSTRACT FROM AUTHOR]

In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer is one of the common malignant tumors with a high incidence and mortality in China. Prognostic biomarkers and potential predictors of the treatment efficacy of gastric cancer urgently need to be identified. Integrin‐β (ITGB) is a superfamily of integrins and is involved in cell adhesion, tissue repair, immune response, and tumor metastasis. Methods: We analyzed ITGB1 expression in our hospital samples of the gastric cancer cohort. And the public data of The Cancer Genome Atlas stomach adenocarcinoma (TCGA‐STAD), The Asian Cancer Research Group (ACRG)/GSE62254, and GSE15459 data sets were analyzed by using the bioinformatic methods. The relationships between ITGB1 expression and clinicopathological features, patient prognosis, activation of the Wnt/β‐catenin signaling pathway, and tumor immunosuppressive factors were also explored. Results: The positive rate of ITGB1 expression in the Fudan University Shanghai Cancer Center gastric cancer tumor tissues was 61.4% (258/420) and correlated with deep invasion (p = 0.017), an advanced clinical stage (p = 0.011), and a poor prognosis (p < 0.05). The TCGA‐STAD/ACRG/GSE15459 cohorts also showed similar results. ITGB1 is one of the upstream molecules of the Wnt/β‐catenin signaling pathway and is correlated with tumor immune suppression. In gastric cancer, we found a correlation between ITGB1 expression and Wnt/β‐catenin signaling pathway activity. In the TCGA‐STAD/ACRG/GSE15459 cohorts, ITGB1 expression was positively associated with immunosuppressive factors and negatively associated with immunoactive factors. Patients with low ITGB1 expression exhibited a significantly high immunotherapy response ratio according to an analysis of tumor immune dysfunction and exclusion (TIDE), which may indicate that ITGB1 is a potential predictor of immunotherapy efficacy. Conclusions: ITGB1 affects the prognosis in gastric cancer patients and plays a core role in immune suppression in gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we first reported the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer patients and assessed predictive ability as a biomarker for different duration adjuvant chemotherapy regimens in the primary cohort and validation cohort Patients with high CXCR6+ TAM infiltration tended to have worse overall survival. A 6-month chemotherapy regimen for high-risk stage II and stage III patients after curative operation benefited those with high CXCR6+ TAM density the most. Furthermore, we found there was a negative relationship between CXCR6+TAMs and activated CD8+ T cells. Cytokines from peripheral blood reflected the immunosuppressive state in patients with high accumulations of CXCR6+TAMs This indicates that CXCR6+TAMs may be involved in the formation of an immunosuppressive environment. We explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360 and 126 consecutive colon cancer patients were enrolled from two medical centers of Zhongshan Hospital. Immunofluorescence and immunohistochemistry were performed to detect the density of CXCR6+TAMs and activated CD8+ T cells. The infiltration of CXCR6+TAMs was higher in tumor tissues and increased with advanced tumor stage. A high density of CXCR6+TAMs predicted worse overall survival (OS) in all CC patients (HR = 2.49, 95% CI = (1.68, 3.70), p < 0.001), and was an independent risk factor verified by Cox regression analysis (HR = 1.68, 95% CI = (1.09, 2.59), p = 0.019). For high-risk stage II and stage III patients with a high density of CXCR6+TAMs, better disease-free survival (DFS) (HR = 0.32, 95% CI = (0.11, 0.89), p = 0.003), and OS (HR = 0.28, 95% CI = (0.07, 1.11), p = 0.014) were observed in the 6-month treatment group. There was a negative relationship between the density of CXCR6+TAMs and CD8+ T cells (R = −0.51, p < 0.001) as well as activated CD8+ T cells (R = −0.54, p < 0.001). Higher levels of IL-6 and lower levels of IL-2R and TNF-α were expressed in high-CXCR6+ TAM-density patients, which indicates that CXCR6+TAMs contribute to an immunosuppressive microenvironment. CXCR6+TAMs predicted prognosis and response to different durations of ACT in CC patients. CXCR6+TAMs were associated with an immunosuppressive microenvironment and suppressed the activation of CD8+ T cells. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought "Yin-Yang theory" in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS. [ABSTRACT FROM AUTHOR]

Lung cancer is increasing every year and it has high morbidity and mortality. Antitumor immunotherapy is a new method for the treatment of lung cancer. Currently, tumor immunotherapy mainly includes classical immunotherapy and immune-targeted therapy To explore the influence of tumor T-lymphocyte (T-cell) infiltration in non-small-cell lung cancer (NSCLC) patients, 100 NSCLC patients diagnosed and treated in Changde Second People's hospital were recruited. Patients were followed up for 3 years. The subjects were divided into a survival group (group S) and a death group (group D). The patient's pathological tissue sections were made, and the degree of T-cell infiltration was counted by H&E (Hematoxylin and eosin) staining. The infiltration degree was graded, and the positive rate of T-cell subsets was calculated by immunohistochemical staining. The 3-year positive rate was 48%, with 48 cases in group S and 52 cases in group D. The positive rate of H&E staining of group S was 100%, including 0 cases of grade 0, 5 cases of grade 1 (10.42%), 16 cases of grade 2 (33.33%), and 27 cases of grade 3 (56.25%). The positive rate of group D was 86.54%, including 4 cases of grade 0 (8.89%), 10 cases of grade 1 (22.22%), 25 cases of grade 2 (55.56%), and 6 cases of grade 3 (13.33%). The total number of T-cell infiltrates in group S was much higher than that in group D (P < 0.05). Immunohistochemical results showed that the mean positive rate of CD8+ T-cell infiltration was 72.1% in group S and 47.6% in group D, with a considerable difference (P < 0.05). No remarkable difference was found in CD4+ and CD25+ (P < 0.05). CD8+ + CD4+, CD8+/CD4+, CD25+/CD8+, CD25+/CD4+, and CD25+/(CD8+ + CD4+) positive rates were calculated, and the difference between group S and group D was substantial in CD8+ + CD4+ (P < 0.05). The results showed that T cells infiltrated by tumors had an immunosuppressive effect on tumor cells. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical features of optic neuritis (ON) complicated with chronic hepatitis B virus (HBV) infection, and evaluate the effectiveness of different treatment regimens, recurrence of ON, visual prognosis, HBV reactivation, liver function and liver structure changes. Methods and Results Total 19 patients (23 eyes) with acute ON complicated with chronic HBV infection admitted to Beijing Tongren Hospital, Capital Medical University from January 2015 to June 2021 were included. There were 13 females and 6 males, 15 cases with monocular onset, 17 cases with unidirectional course of disease, and 6 cases with optic disc edema. The time to the worst visual acuity (peak time) was 3 (2, 7) d after onset, and 16/23 eyes had severe visual impairment. Enhanced MRI showed abnormal intensity in orbital, intraductal or intracranial segments of optic nerve, even involving optic nerve sheath and optic chiasm. Anti-nuclear antibody (ANA) was positive in 5 cases and A type Sjögren's syndrome antibody (SSA) was weakly positive in one case. Cerebrospinal fluid (CBF) pressure decreased in 1/7 cases and white blood cell count increased in 2/7 cases. HBV DNA positive group (HBV DNA ≥ 100 IU/ml, 10 cases and 11 eyes) had more severe visual impairment than negative group (HBV DNA < 100 IU/ml, 9 cases and 12 eyes), the difference was statistically significant (Fisher's exact probability: P = 0.005, 0.003). HBV DNA positive group was treated with entecavir, and the recurrence of ON was ignored during follow-up. HBV DNA negative group didn't receive antiviral therapy, one case progressed to cirrhosis, 3 cases had abnormal liver function, and 2 cases had HBV reactivation. Conclusions The visual function of patients with ON complicated with chronic HBV infection was seriously impaired, and the response to glucocorticoid therapy was not good. The visual impairment of patients with positive HBV DNA was more serious than patients with negative HBV DNA. Patients with ON complicated with chronic HBV infection should be treated with antiviral drugs in combination with glucocorticoid therapy. [ABSTRACT FROM AUTHOR]

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Simple Summary: Since PCV2 is currently the primary viral agent in intensive pigs, the cost of immune suppression and preventative measures has resulted in severe economic losses. It has been claimed that PCVs infect wild pigs in a number of nations, including South Korea, Germany, and Italy. Jiangxi province in China is a heavily populated area with an extremely intensive pig production industry, but data on the transmission of PCVs in wild boar are poor. In order to ascertain the incidence of PCV1/2/3 and the genetic characteristics of PCV2 circulating in wild boar in Jiangxi province, an epidemiological investigation was conducted. We discovered a medium prevalence of PCVs, notably PCV2, which indicated that wild boar in Jiangxi province were exposed to PCVs. Our findings highlight the need for the pig sector to actively prevent the contact between livestock and wild boar, which have a high risk of PCVs infection. A number of disorders that harm pig production are linked to porcine circoviruses, including PCV2. PCV2 infection is a substantial contributor to porcine-circovirus-associated illnesses (PCAS) and the post-weaning multi-systemic wasting syndrome (PMWS), which have a significant negative economic impact on pig production. Additionally, PCV infection has been labeled as a global concern to cattle and wildlife. This study's objectives were to examine the prevalence of PCV1/2/3 in Jiangxi Province, China, and to clarify the epidemiological significance of wild boar in PCV epidemiology. The 2020 hunting seasons resulted in the collection of 138 wild boar samples for PCV1/2/3 detection, which was followed by the genetic clarification of PCV2 strains. According to our data, 21.7% (30/138) of the population had PCV1 positivity, 22.5% (31/138) had PCV2 positivity, and 5.8% (8/138) had PCV3 positivity. Additionally, 10 out of 138 wild boar samples had PCV1 and PCV2 co-infections, while 5 out of 138 wild boar samples had PCV2 and PC3 co-infections. Nineteen full-length PCV2 genomes measuring 1767 nt were recovered from various animal tissues using conventional PCR. Eighteen out of nineteen PCV2 strains were identified as PCV2b by phylogenetic tree analysis, which was completed by the reference strain HLJ2015 obtained from domestic pigs in 2015. Additionally, one genotype of PCV2d JX11-2020 (MW889021) shared a sub-branch with the referenced strain TJ (AY181946), which was isolated in domestic pigs in 2002. This finding raises the possibility that domestic pigs could contract PCV2 strains from wild boar, posing a serious threat to the Jiangxi province of China's pig production industry. [ABSTRACT FROM AUTHOR]

Background: Severe community-acquired pneumonia (SCAP) is the main cause of mortality in immunocompromised patients. Compared with conventional microbiological tests (CMT), metagenomic next-generation sequencing (mNGS) can quickly and simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased manner. It is increasingly used for severe respiratory infectious diseases, especially for immunocompromised patients. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes in immunocompromised patients with SCAP have not been evaluated. Methods/Design: The MATESHIP study is a prospective, multicenter, parallelgroup, open-label, randomized controlled trial from 20 ICUs in university hospitals and academic teaching hospitals across Shandong Province, China. We will enroll 342 immunocompromised patients with early onset SCAP who are admitted to an intensive care unit (ICU). Participants will be randomly allocated to an mNGS-guided treatment group or a conventional treatment group (guided by CMT), according to centrally computer-based block randomization stratified by participating centers. Participants will undergo CMT tests using appropriate lower respiratory tract (LRT) and other necessary specimens, with or without mNGS tests using LRT specimens. The primary outcomes will be: (1) The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death; and (2) the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses). The secondary outcome measures will be: days from randomization to initiation of definitive antimicrobial treatment; overall antimicrobial agent use and cost; total cost of hospitalization; length of ICU stay; 28- and 90-day mortality; and clinical cure rate. This study hypothesizes that mNGS-guided treatment will decrease the degree of organ dysfunction/failure, the consumption of antimicrobial agents, and mortality, while the cure rate will be increased, and the time to initiation of appropriate therapy will be advanced. Discussion: The MATESHIP study will evaluate for the first time whether mNGS-guided antimicrobial therapy improves the outcomes of SCAP in an immunocompromised population, and provide high-level evidence on the application of mNGS in the management of this population. [ABSTRACT FROM AUTHOR]

Background: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. Methods: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. Results: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non‐immunosuppression and immunosuppression groups, respectively. Relative to non‐immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable‐adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18–0.40; p < 0.001) and IPTW‐weighted Cox model (HR 0.28; 95% CI 0.19–0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1‐month increase; 95% CI 0.87–0.92; p < 0.001; IPTW‐adjusted). Combination therapy with steroids and non‐steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07–0.26; p < 0.001). Conclusion: Immunosuppression significantly reduced the 2‐year risk of generalization in patients with OMG. [ABSTRACT FROM AUTHOR]

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Background: Compared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population. Methods: We analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015–2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors. Results: The most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine. Conclusion: Fever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients. [ABSTRACT FROM AUTHOR]

What is known and objective: Tacrolimus (FK506), an effective and potent calcineurin inhibitor, is the cornerstone of immunosuppression after kidney transplantation. Wuzhi capsule (WZC), a prescribed ethanol extract of Nan‐Wuweizi (Schisandra sphenanthera), is widely prescribed for kidney transplant recipients for the maintenance of tacrolimus concentration in clinical settings. Previous studies have demonstrated that WZC can increase the blood concentration of tacrolimus. However, it remains controversial whether to use WZC can be used to increase tacrolimus concentration in clinical practice. Our study aimed to evaluate the efficacy and safety of WZC combined with tacrolimus in the treatment of kidney transplant recipients. Methods: One hundred and ninety four Chinese kidney transplant recipients were included in this retrospective study. The recipients were divided into two groups (non‐WZC group and WZC group). We investigated the effects of WZC on tacrolimus in terms of tacrolimus metabolism, laboratory tests, pharmacogenomics, renal function and adverse reactions. Results and Discussion: The concentration/dose (C0/D) of tacrolimus was significantly higher in the WZC group than the non‐WZC group. The laboratory findings of blood routine tests, liver and kidney function were not significantly different between the two groups. The CYP3A5 genotype showed clearly associated with tacrolimus C0/D, whereas no significant difference was observed in patients with CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. The improvement of C0/D by administration of WZC was significant in CYP3A5 expressers compared to non‐expressers. Furthermore, the WZC group had a remarkably higher proportion of subjects who reached the target tacrolimus concentration than the non‐WZC group. No significant differences in renal function and adverse reactions were observed between the groups. What is new and conclusion: Wuzhi capsule can increase tacrolimus concentration without negative effects on renal function and adverse reactions, especially in CYP3A5 expressers. Efficient and economical synergistic effects can be achieved by the combined administration of WZC in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic., Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records., Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection ( p  < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p  = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p  < 0.001) emerged as independent risk factors for early MG exacerbation., Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xu, Qin, Liu, Guo, Huang, Fan, Zhang, Qi, Zhang, Yang, Shi and Yang.)

Background: Septic patients with persistent lymphopenia may be in an immunosuppressed state. Therefore, we evaluated and compared the clinical characteristics and outcomes of septic patients with persistent lymphopenia (≥2d) and those with nonpersistent lymphopenia. Methods: A retrospective cohort study was designed. A total of 1306 patients with sepsis who were attended to the First Affiliated Hospital of Dalian Medical University from March 2016 to August 2022 were included. The primary clinical outcome was 90d mortality. The secondary clinical outcomes were the length of stay, hospital mortality, 28d mortality, the incidence of secondary infection, and differences in clinical characteristics. Results: Among 1306 patients with sepsis, 913 (69.9%) patients developed persistent lymphopenia. Compared with patients with nonpersistent lymphopenia, patients with persistent lymphocytopenia were admitted to intensive care unit (75.7% vs 52.7%, P  <   .05), treated with mechanical ventilation (67.6% vs 39.2%, P  < .05), positive rate of microbial culture pathogens (86.7% vs 71.2%, P  <   .05), SOFA [8.0 (6.0-10.0) vs 6.0 (4.0-8.0), P  < .05], length of stay [17.0d (12.0-27.0) vs 13.0d (10.0-21.0), P  < .05], hospital mortality (37.7% vs 24.2%, P  < .05), 28d mortality (38.0% vs 22.9%, P  < .05), and 90d mortality (51.2% vs 31.3%, P  < .05) were higher. As the duration of lymphocytopenia increased, so did the mortality rate in hospital. In addition, the onset time of persistent lymphopenia was not associated with SOFA. But we found that the frequency of persistent lymphopenia during hospitalization was positively associated with SOFA. Conclusion: Septic patients with persistent lymphopenia have higher mortality, worse conditions, increased risk of secondary infection, and poor prognosis regardless of shock., Competing Interests: Authors’ NoteEthics Statement: This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (no. PJ-KS-KY-2022-357) with waiver of written consent. Availability of Data and Materials: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection in idiopathic membranous nephropathy (IMN) patients, who are treated with immunosuppressive drugs. However, the risk factors of infection and their prognosis are rarely investigated. We aimed to characterize the clinical manifestations of PCP in patients with IMN, and to understand their risk factors, so that we can provide early warnings to patients with high risk and potential poor prognosis. We conducted a retrospective observational study of IMN patients in a referral center in China, from Jan 2012 to Dec 2018. Clinical and laboratory data were collected separately at the time of IMN and PCP diagnosis. Patients with PCP were matched to those without by gender and age at a ratio of 1:4. The risk factors and prognostic factors were determined by univariate and multivariate logistic regression analysis. A total of 879 patients with IMN were included, with a median follow-up of 267 (interquartile range (IQR) 64,842) days. In total, 26 (2.96%) of them were diagnosed with PCP. The infection rate increased to 3.87% among patients who received corticosteroids, and it further increased to 5.49% in those received over 0.5mg/kg prednisone. Univariate analysis indicated that initial usage of corticosteroids, use of cyclophosphamide, reduced estimated glomerular filtration rate (eGFR), and higher 24-h proteinuria were related to the PCP susceptibility. Multivariate analysis revealed that corticosteroid treatment and reduced eGFR increased the risk of the Pneumocystis jirovecii infection. The case fatality rate of the PCP patients was 23.08%, and increased to 75% among patients requiring invasive ventilation. Univariate analysis indicated that pulmonary insufficiency, invasive ventilation, decreased eGFR, and increased lactate dehydrogenase at presentation were linked to poor prognosis. PCP is not rare in patients with IMN, especially those on corticosteroids, and presented with decreased eGFR. Considering the high case fatality rate, further studies are in need for prevention and management of these patients. [ABSTRACT FROM AUTHOR]

Combination of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various tumors. However, the combination might be associated with increased cardiotoxicities. Myocarditis is a potentially fatal complication in cancer patients treated with ICI. Currently, there are no clear guidelines for the management of this disease nor data characterizing the clinical course of myocarditis patients due to the combination of ICI and anti-VEGF therapy. This study included all patients consecutively admitted to Shanghai Zhongshan Hospital, Fudan University for the diagnosis of ICI-associated myocarditis according to Bonaca's criteria. The clinical presentation and outcome of myocarditis patients were collected receiving ICI and anti-VEGF combined therapy. A total of 48 patients were included (23 received combined treatment of ICI and anti-VEGF while 25 received ICI only). No differences in baseline characteristics, clinical course, and outcomes were observed among patients receiving ICI with or without anti-VEGF treatment. The patients were subdivided into 3 groups including 8 fulminant cases, 25 clinically significant cases, and 15 subclinical cases based on clinical severity. The fulminant group was associated with a higher rate of cardiovascular deaths (CVDs) compared with clinically significant and subclinical groups (87.5% versus 4.0% versus 0.0%, p < 0.01). When stratified by the dose of corticosteroids used, cases with high-dose usage were more likely to have a CVD when compared to low dose or no use and intermediate dose groups (0.0% versus 4.0% versus 57.1%, p < 0.01). No significant differences between myocarditis patients receiving ICI or combined anti-VEGF therapy in terms of clinical presentation and outcome were observed. Treatment strategy for myocarditis in patients using ICI or combined anti-VEGF therapy should be based on clinical severity. Specifically, immunosuppressive therapy besides high-dose corticosteroids is needed for fulminant cases. • Describing the clinical course of ICI combined with anti-VEGF related myocarditis. • Patients who received combined therapy may develop a severe form of myocarditis. • Use of steroids for myocarditis patients should be guided by clinical severity. • Intensified therapy besides high-dose steroids is needed for fulminant cases. [ABSTRACT FROM AUTHOR]

Objective: Patients with non-small cell lung cancer (NSCLC) respond differently to cytokine-induced killer cell (CIK) treatment. Therefore, potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated. The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC. Methods: Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital. We performed whole-exome sequencing (WES) on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC, and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment. Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance. WES and RNA-seq data between lung squamous cell carcinoma (SCC) and adenocarcinoma (Aden) were analyzed and compared. Results: The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS, as analyzed by multivariate Cox proportional hazard regression (P = 0.031). The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment. Relatively low expression of HLA class II genes and checkpoint molecules, and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC. Conclusions: Coordinated suppression of the expression of HLA class II genes and checkpoint molecules, as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden. [ABSTRACT FROM AUTHOR]

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear. Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated. Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups. Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is an acute, highly contagious, and deadly infectious disease. The mortality rate of the most acute and acute ASF infection is almost 100%. The World Organization for Animal Health [Office International des épizooties (OIE)] lists it as a legally reported animal disease and China lists it as class I animal epidemic. Since the first diagnosed ASF case in China on August 3, 2018, it has caused huge economic losses to animal husbandry. ASF is caused by the African swine fever virus (ASFV), which is the only member of Asfarviridae family. ASFV is and the only insect-borne DNA virus belonging to the Nucleocytoplasmic Large DNA Viruses (NCLDV) family with an icosahedral structure and an envelope. Till date, there are still no effective vaccines or antiviral drugs for the prevention or treatment of ASF. The complex viral genome and its sophisticated ability to regulate the host immune response may be the reason for the difficulty in developing an effective vaccine. This review summarizes the recent findings on ASFV structure, the molecular mechanism of ASFV infection and immunosuppression, and ASFV-encoded proteins to provide comprehensive proteomic information for basic research on ASFV. In addition, it also analyzes the results of previous studies and speculations on the molecular mechanism of ASFV infection, which aids the study of the mechanism of clinical pathological phenomena, and provides a possible direction for an intensive study of ASFV infection mechanism. By summarizing the findings on molecular mechanism of ASFV- regulated host cell immune response, this review provides orientations and ideas for fundamental research on ASFV and provides a theoretical basis for the development of protective vaccines against ASFV. [ABSTRACT FROM AUTHOR]

Background: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. Results: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. Conclusions: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The emergence of hepatitis B surface antigen in a patient with previously negative hepatitis B virus (HBV) serology post‐orthotropic liver transplant (OTLX) is known as de novo hepatitis B (DNHB). As there are no data on patients with DNHB available from Qatar, we aim to do a pioneer study indexing their clinical profile and epidemiology of patients with DNHB in Qatar. Materials and Methods: This descriptive epidemiological study was done by retrospectively reviewing records of 159 post‐OTLX patients. HBV serology of these patients post‐OTLX was reviewed, and 17 were identified as DNHB cases. Baseline epidemiological characteristics were defined and compared between DNHB cases and the rest. DNHB cases were analyzed statistically using the chi‐square test and Kaplan‐Meier curve. Results: The majority of the subjects were men (65%) and Qataris (40%). Mean age was 57.4 ± 12.5 years. Bulk of them underwent OTLX in China (44%). The overall incidence of DNHB was 10.7%, with transplants in China having significantly higher incidence than transplants from all other countries. The mortality rate was 23.5% in DNHB cases compared to 2.8% in non‐DNHB. 67% of patients survived at least 64 months after the diagnosis of DNHB. Five‐year survival did not vary significantly between those with DNHB and those without. Conclusion: Orthotropic liver transplant in centers selecting donors liberally without screening for HBV poses the risk of DNHB. We recommend having protective levels of HBs antibodies before OTLX. Prophylactic antiviral treatment should be considered until peri‐operative HBV transmission has been excluded by screening hepatic tissue for HBV DNA. [ABSTRACT FROM AUTHOR]

Objective: To present the first live birth after uterine transplantation (UTx) in the People's Republic of China.Design: Case study.Setting: University hospital.Patient(s): A 22-year-old woman with Mayer-Rokitansky-Kuster-Hauser syndrome and previous surgery for vaginal reconstruction and UTx.Intervention(s): Endometrial preparation, frozen embryo transfer, pregnancy follow-up, and cesarean section.Main Outcome Measure(s): Results of in vitro fertilization, frozen embryo transfer, ultrasound measurements during pregnancy, rejection diagnosis and treatment, delivery, live birth, and histology of uterus.Results(s): Frozen embryo (cleavage stage) transfer started 1.5 years after UTx. The first embryo transfer (n = 2) resulted in a biochemical pregnancy. The second, third, and fourth embryo transfer (n = 2, 2, 3) did not result in pregnancy. The fifth embryo transfer (n = 3) resulted in pregnancy with two gestational sacs, but with spontaneous disappearance of one in early pregnancy. During early pregnancy three episodes of vaginal bleedings occurred (gestational weeks 6 + 2, 13 + 1, and 16 + 3), with a spontaneously resorbing subchorionic hematoma diagnosed at the last bleeding episode. Bleeding episodes were treated with corticosteroids and tacrolimus. During pregnancy, blood flow velocity waveforms and fetal growth parameters were normal. A subacute cesarean section was performed at gestational week 33 + 6 due to uterine contraction pattern suggesting imminent labor. A healthy boy (2,000 g) with Apgar scores of 10, 10, 10 was delivered. The uterus was kept for a possible second pregnancy.Conclusion(s): The first live birth after UTx in the People's Republic of China is reported and this occurred after a robotic-assisted laparoscopic uterus retrieval from the mother. [ABSTRACT FROM AUTHOR]

Since the first description of infections with severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) in China in December 2019, it has evolved into a pandemic and emerged as an unprecedented worldwide crisis overwhelming healthcare systems globally. Analysis of the available literature to date suggests that, in addition to older age, patients with underlying co-morbidities including hypertension, diabetes, heart disease are at higher risk for severe disease with increased mortality. Practitioners around the world also have become increasingly concerned that immunosuppressed patients including those with autoimmune diseases may be at increased risk for developing Coronavirus Disease 2019 (COVID-19) with serious complications. Very little is known about how anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis modifies the susceptibility, clinical presentation and disease course of COVID-19. In this review, we discuss the mechanism of action and challenges of the current therapeutic armamentarium of ANCA-associated vasculitis and outline approaches to management of ANCA-associated vasculitis during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Antithymocyte globulin (ATG) is widely used for allogeneic haematopoietic stem cell transplantation (allo-HSCT) in severe aplastic anaemia (SAA). Only rabbit-ATG (r-ATG) and porcine-antilymphocyte globulin (p-ALG) are available in China, but the p-ALG-containing conditioning regimen for allo-HSCT in SAA has seldom been reported. In this study, we retrospectively evaluated the outcomes of 41 SAA patients receiving allo-HSCT with a p-ALG-containing conditioning regimen in our transplantation centre. All patients engrafted, and no death during conditioning was observed. The actuarial 3-year overall survival (OS) rates were 95.1 ± 3.4%. The actuarial 3-year disease-free survival (DFS) rates were 85.0 ± 5.7%. Acute graft-versus-host disease (aGVHD) predicted inferior OS (p < 0.05). The interval from diagnosis to transplantation for more than 100 days predicted an inferior DFS rate (p < 0.05) and a higher graft rejection/poor graft function (GR/PGF) rate (p < 0.01). In conclusion, the p-ALG-containing regimen showed satisfactory effects and safety in allo-HSCT for SAA patients. P-ALG could be a potential alternative preparation for r-ATG in SAA allo-HSCT. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding social support in patients is mostly from cross-sectional studies. Very few studies have focused on the change in social support systems before and after hematopoietic stem cell transplantation.Methods: A total of 191 patients were investigated before transplantation and at 30, 90 and 180 days post-transplantation. The social support for patients was evaluated by the Perceived Social Support Scale (PSSS).Results: The overall PSSS scores showed a continuous decline in means from 71.29 ± 9.73 before the transplantation to 69.44 ± 10.61, 68.73 ± 10.04, and 66.37 ± 12.02 at 30, 90 and 180 days post-transplantation, respectively. In comparison to the baseline, the overall PSSS scores decreased significantly at 90 and 180 days post-transplantation (P < .05). The Generalized Estimated Equation (GEE) analysis found that patients with no transplant-related complications, higher household income, and better educational status had preferable social support.Conclusion: Social support presented a marked downward trend during the six month period. Patients with no transplant-related complications, higher household income and better educational status had preferable social support. Therefore, social support as a high-priority quality of life should be given close attention in the early phase of transplantation. Positive measures should be taken to improve social support in the early phase of transplantation especially among individuals undergoing this procedure for the first time. [ABSTRACT FROM AUTHOR]

Summary: Serpins are evolutionarily conserved serine protease inhibitors that are widely distributed in animals, plants and microbes. In this study, we reported the cloning and functional characterizations of two novel serpin genes, HlSerpin‐a and HlSerpin‐b, from the hard tick Haemaphysalis longicornis of China. Recombinant HlSerpin‐a and HlSerpin‐b displayed protease inhibitory activities against multiple mammalian proteases. Similar to other tick serpins, HlSerpin‐a and HlSerpin‐b suppressed the expression of inflammatory cytokines such as TNF‐α, interleukin (IL)‐6 and IL‐1β from lipopolysaccharide‐stimulated mouse bone‐marrow‐derived macrophages (BMDMs) or mouse bone‐marrow‐derived dendritic cells (BMDCs). The minimum active region (reaction centre loop) of HlSerpin‐a, named SA‐RCL, showed similar biological activities as HlSerpin‐a in the protease inhibition and immune suppression assays. The immunosuppressive activities of full‐length HlSerpin‐a and SA‐RCL are impaired in Cathepsin G or Cathepsin B knockout mouse macrophages, suggesting that the immunomodulation functions of SA and SA‐RCL are dependent on their protease inhibitory activity. Finally, we showed that both full‐length HlSerpins and SA‐RCL can relieve the joint swelling and inflammatory response in collagen‐induced mouse arthritis models. These results suggested that HlSerpin‐a and HlSerpin‐b are two functional arthropod serpins, and the minimal reactive peptide SA‐RCL is a potential candidate for drug development against inflammatory diseases. [ABSTRACT FROM AUTHOR]

Summary: Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty‐seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow‐up. The mean age for the survivors [51 years (IQR, 35–65 years)] was significantly lower than that of the non‐survivors [79 years (IQR, 67–86 years)] (P < 0·001). Overall survival was higher in non‐malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913–1·889, P = 0·015). [ABSTRACT FROM AUTHOR]

In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5–58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5–48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ −0.163. The predictive value was validated internally and externally. Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy. [Display omitted] • Combining ursodeoxycholic acid with immunosuppressants improves outcomes in primary biliary cholangitis with moderate-to-severe interface hepatitis. • Baseline IgG>1.3×ULN and ALP<2.4×ULN predict fibrosis regression. • A developed Fibrosis Regression Score (FRS), incorporating IgG and ALP, identifies individuals achieving fibrosis regression. [ABSTRACT FROM AUTHOR]

Background: Interleukin-35 (IL-35) is a recently discovered cytokine that plays a role in immune suppression and has therefore been the subject of a great deal of research. A bibliometric analysis of the global research concerning IL-35, however, is rare. Objectives: The aim of this research was to assess the international scientific output of IL-35 research and explore its hotspots and frontiers from 2009 to 2018 by bibliometric analysis. Methods: Publications about IL-35 research from 2009 to 2018 were retrieved from the Web of Science Core Collection (WoSCC). Citespace V was used to analyze years, journals, countries, research institutions, areas of exploration, research hotspots, and trends of publication. Results: We retrieved a total of 416 publications and observed a trend of publications increasing over the past decade. Original articles (351) were the most frequently occurring document type. The largest number of publications belonging to one country and one institution, respectively, was China (202) and Tianjin Medical University (17). Trending keywords may indicate frontier topics, including “infectious tolerance,” “autoimmune,” and “central nervous system.” Conclusion: This study provides valuable information on the study of IL-35 so that researchers may identify new research fields. [ABSTRACT FROM AUTHOR]

Objectives: The standard strategy for treating lupus nephritis comprises glucocorticoids together with either intravenous cyclophosphamide or oral mycophenolate mofetil, but the low remission rate is still a challenge in practice. This study was aimed to seek higher remission rate of lupus nephritis using a combined strategy.Method: A 24-week trial was conducted in 17 rheumatology or nephrology centers in China. A total of 191 lupus nephritis patients were randomized to follow a combined immunosuppressive treatment (CIST) with intravenous cyclophosphamide, an oral immunosuppressive agent, namely mycophenolate mofetil, azathioprine or leflunomide, and hydroxychloroquine (n = 95), or receive intravenous cyclophosphamide alone (n = 96) for 24 weeks. Glucocorticoid was given to both groups. The primary end point was a complete remission with a most stringent standard as proteinuria < 150 mg per 24 h, normal urinary sediment, serum albumin, and renal function at 24 weeks. The secondary end point was treatment failure at 24 weeks.Results: At week 24, both the rate of complete remission (39.5%) and total response (87.2%) was higher in the combined group, compared with CYC group (20.8% and 68.8%, p < 0.05). The cumulative probability of complete remission was also higher in the combined group (p = 0.013). In addition, the combined treatment was superior to routine CYC with less treatment failure (12.8% vs.31.2%, p < 0.001). No difference was found between the incidences of severe adverse events in the two arms: 3.2% (3/95 combined group) vs.4.2% (4/96 CYC group).Conclusion: Treatment with a combined immunosuppressive agent is superior to routine CYC only therapy in lupus nephritis. [ABSTRACT FROM AUTHOR]

Highlights • Novel variant IBDVs were first identified in China.. • The Chinese novel variant IBDVs were obviously different from the American variant IBDV.. • The serious threat of the variant IBDV to chicken was further confirmed by animal experiments. Abstract Infectious bursal disease (IBD) is one of the most important immunosuppressive diseases that seriously threaten poultry farming and food safety worldwide. The variant strain of infectious bursal disease virus (IBDV) has been greatly neglected for more than 30 years. Recently, the subclinical infection of suspected IBD, causing considerable economic losses, occurred in the main chicken-farming regions of China. Through RT-PCR, sequencing, and phylogenic analyses, novel variant IBDVs were first identified in six provinces of eastern China. Immunological detection further confirmed the antigenic variation of the Chinese variant IBDVs. The Chinese IBDV variants were obviously different from the American IBDV variants, with less than a 97.7% (VP1) or 98.7% (VP2) amino acid sequence identity. Animal experiments further confirmed the serious threat of the variant IBDVs to chickens, demonstrating irreversible damage to the central immune organ, obvious immunosuppression, and growth retardation. This study not only identified the pandemic nature of the novel variant IBDVs for the first time but also discovered the distinct molecular epidemiological characteristics of these viruses, which will contribute more to the control of the disease. [ABSTRACT FROM AUTHOR]

Aim: To investigate the potential impact of single-nucleotide polymorphisms (SNPs) in the FK506-binding protein (FKBP)-calcineurin (CaN)-nuclear factor of activated T cells (NFAT) signaling pathway on the efficacy and safety of tacrolimus (TAC) in Chinese renal transplant patients.Methods: Seventy-seven tag SNPs were detected in 146 patients who were on TAC-based maintenance immunosuppression and who followed up for at least 2 years. The relationships of these polymorphisms with clinical outcomes such as acute rejection, acute nephrotoxicity, pneumonia, and estimated glomerular filtration rate (eGFR) were explored. For the FKBP1A rs6041749 polymorphism, which has a significant association with renal function over time, a preliminary functional analysis was performed using a dual-luciferase reporter gene system.Results: The patients with FKBP1A rs6041749 TT genotype had a more stable eGFR level than CC and CT carriers (P = 2.08 × 10−8) during the 2 years following transplantation. Dual-luciferase reporter assay results showed that the rs6041749 C variant could enhance the relative luciferase activity compared with the T variant, which indicated that the rs6041749 C allele may increase the FKBP1A gene transcription. In addition, we did not find any association between these genetic variants and the risk of acute rejection, acute nephrotoxicity, and pneumonia in renal transplant patients receiving TAC-based immunosuppression.Conclusions: FKBP1A rs6041749 C allele carriers are at higher risk for eGFR deterioration. The variant might serve as a biomarker to predict allograft function in renal transplant patients. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for patients with leukemia. However, relapse remains the leading cause of death after transplantation. In recent years, substantial progress has been made by Chinese physicians in the field of establishment of novel transplant modality, patient selection, minimal residual disease (MRD) monitoring, and immunological therapies, such as modified donor lymphocyte infusion (DLI) and chimeric antigen receptor T (CART) cells, as well as MRD-directed intervention for relapse. Most of these unique systems are distinct from those in the Western world. In this consensus, we reviewed the efficacy of post-HSCT relapse management practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association, and compared these studies withthe consensus or guidelines outside China. We summarized the consensus on routine practices of post-HSCT relapse management in China and focused on the recommendations of MRD monitoring, risk stratification directed strategies, and modified DLI system. This consensus will likely contribute to the standardization of post-HSCT relapse management in China and become an inspiration for further international cooperation to refine global practices. [ABSTRACT FROM AUTHOR]