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Background: Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer. Methods: Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis. Result: The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5. Conclusion: In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1–3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203–89 605) ng/mL at diagnosis, 48 189.4 (15 537–83 375) ng/mL before IVCY therapy, and 10 721.2 (5637–13 245) ng/mL at the end of IVCY therapy (P <.05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896–45 626) ng/mL, and to 37 464.2 (19 872–58 321) ng/mL at 24 months (P <.05). Five patients discontinued antimicrobial therapy within 3–12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers. [ABSTRACT FROM AUTHOR]

Background: Anti-IFN-γ autoantibodies (AIGAs) are closely related to the disseminated infection of multiple pathogens. Mycobacterium phlei (M. phlei) is a nonpathogenic nontuberculous mycobacteria (NTM), and M. phlei infection of the bone is extremely rare. We report a rare case of high-titer AIGAs presenting with Sweet's syndrome (SS) accompanied by opportunistic coinfection with multiple pathogens during 12 years of follow-up. The patient in this case also developed disseminated M. phlei infection with osteolytic destruction after treatment for SS. Case Presentation: A 68-year-old Chinese woman was admitted to our hospital in August 2009 due to fever and cough with expectoration for 3 months. The patient was successively infected with Klebsiella pneumoniae, herpes zoster virus and Candida. Chest computed tomography (CT) showed recurrent consolidations in different lung fields. After 15 months of antimicrobial treatment, the patient experienced partial recovery. In September 2010, the patient was pathologically diagnosed with SS due to the presence of multiple rashes. After prednisone and thalidomide treatment, the rashes subsided, and the pulmonary lesions had completely absorbed. In May 2011, the patient was diagnosed with disseminated tuberculosis and was administered anti-tuberculosis therapy for 3 months without improvement. NTM was subsequently cultured from her sputum and chest wall pus, and she improved after 20 months of anti-NTM therapy. In March 2016, the patient developed osteolytic destruction of the C7-T2 vertebral bodies with a back abscess. NTM was eventually cultured from the dorsal abscess pus and further identified as M. phlei. High-titer AIGAs were detected in the patient's serum. After another round of aggressive anti-NTM therapy, the patient was finally cured. Conclusion: Patients with AIGA-associated anti-cytokine autoantibody disease can present with multiple opportunistic infections and SS involving the lung. AIGA-associated immunodeficiency leads to infection with nonpathogenic M. phlei, which is refractory, can cause relapse, and even leads to osteolytic destruction. [ABSTRACT FROM AUTHOR]

Purpose: Disseminated nontuberculous mycobacterial (DNTM) infection can involve multiple organs, including the lungs, skin and soft tissues and lymph nodes. However, NTM infection leading to osteolysis has been rarely reported. Here, we analyzed the clinical features, osteolytic mechanisms, treatment and prognosis of patients with DNTM disease with osteolytic lesions. Patients and Methods: This retrospective study was conducted between January 1, 2011, and December 31, 2020, at the First Affiliated Hospital of Guangxi Medical University and the Fourth People's Hospital of Nanning City. Patients who had culture and/or histopathological proof of DNTM disease with osteolytic lesions were included. Results: Ten HIV-negative patients with DNTM disease with osteolytic lesions were enrolled. Five of these patients had underlying diseases. Seven and three of the patients were positive and negative for anti-interferon-γ autoantibodies (AIGAs), respectively. The AIGA positivity rate was 70% (7/10). Ostealgia and anemia were the most common symptoms, followed by fever, emaciation, cough, expectoration, anorexia, subcutaneous abscesses and lymphadenopathy. Leukocyte and neutrophil counts were increased. The most common sites were the vertebrae, sternum, clavicle and ribs, although the femur, ilium, humerus, and scapula were also involved. Radiography and computed tomography (CT) showed moth-eaten or irregular destruction of bone, bone defects, pathological fracture, periosteal proliferation and surrounding abscesses. Emission CT (ECT) bone scans showed significantly increased uptake in many skeletal regions. Positron emission tomography(PET)/CT showed metabolic activity in multiple bones. All patients received anti-nontuberculous therapy, and five underwent surgery. Two died during treatment. Conclusion: DNTM infection of bone and leading to osteolysis usually occurs in patients with AIGA-positive antibodies. DNTM disease with osteolysis is characterized by increased leukocytes and neutrophil counts, focal suppurative granulomas, and multiple areas with moth-eaten or irregular destruction of bone with increased radioactive concentrations. Early diagnosis and timely, effective combination anti-NTM therapy can improve the prognosis. [ABSTRACT FROM AUTHOR]

A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces marneffei and Burkholderia cepacia infection. The patient's lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections. [ABSTRACT FROM AUTHOR]

Background: Anti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data., Methods: This systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity., Results: We included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%)., Conclusions: Intracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei , and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases., 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 © 2022 Qiu, Fang, Ye, Zeng, Tang, Wei, Yang, Li and Zhang.)