A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Immunoglobulin G4-related disease (IgG4-RD) is a rare systemic immune-mediated disorder characterized by infiltration of IgG4-positive plasma cells and multiorgan fibrosis. Among them, cases with multiple pancreatic cystic lesions as the prominent manifestation are relatively rare, and they are easily misdiagnosed as pancreatic tumors or pancreatitis in clinical practice. Herein, we report one patient with IgG4-RD admitted to Peking Union Medical College Hospital. The patient initially presented with multiple pancreatic cystic lesions and aneurysmal dilatation of the abdominal aorta, accompanied by markedly elevated serum IgG4 levels. Combined with pathological findings from submandibular gland biopsy, the diagnosis of IgG4-RD was ultimately established. After treatment with a regimen of glucocorticoids combined with cyclophosphamide, the patient′s condition improved. Meanwhile, we performed a literature review of cases with IgG4-RD-related pancreatic cystic lesions, aiming to improve clinicians′ understanding of this rare disease phenotype.

Hypocomplementemic urticarial vasculitis (HUV) is a rare autoimmune disorder characterized by recurrent urticarial eruptions, hypocomplementemia and systemic involvement. This disease is prone to misdiagnosis, and its systemic manifestations may include arthritis, abdominal pain, renal involvement, chronic obstructive pulmonary disease and so on. Herein, we report a case of HUV presenting with recurrent abdominal pain, generalized wheals and arthralgia. Laboratory tests revealed decreased complement levels, skin histopathology was consistent with leukocytoclastic vasculitis, and imaging examinations indicated spondyloarthritis, thus confirming the diagnosis of HUV. The patient initially received systemic glucocorticoids combined with colchicine, whereas recurrent rash and arthralgia persisted. Tofacitinib (a Janus kinase inhibitor) and methotrexate were subsequently added to the regimen, leading to remission of symptoms. This case suggests that tofacitinib may serve as a potential therapeutic alternative for patients with HUV who respond poorly to glucocorticoids.

Background::Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’ clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.Methods::We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results::We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). Conclusions::Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.Trial Registration::ClinicalTrials. gov, NCT01670695.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.
Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Plant Extracts/metabolism* ; Lipopolysaccharides/pharmacology* ; Macrophages ; Cytokines/metabolism* ; RNA, Messenger/metabolism*

OBJECTIVE: To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism (CH). METHODS: Whole exome sequencing (WES), copy number variation (CNV) sequencing and chromosomal microarray analysis (CMA) were carried out for a newborn infant who had presented at Linyi People's Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review. RESULTS: The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents. CONCLUSION Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.
Female ; Humans ; Congenital Hypothyroidism/genetics* ; DNA Copy Number Variations ; Phenotype ; Syndrome ; Microarray Analysis

This study identified the anti-depression targets of Kaixin San(KXS) in the brain tissue with "target fishing" strategy, and explored the target-associated pharmacological signaling pathways to reveal the anti-depression molecular mechanism of KXS. The Balb/c mouse model of depression was established by chronic unpredictable mild stress(CUMS) and the anti-depression effect of KXS was evaluated by forced swimming test and sucrose preference test. KXS active components were bonded to the benzophenone-modified magnetic nanoparticles by photocrosslinking reaction for capturing target proteins from cortex, thalamus and hippocampus of depressive mice. The target proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS). The enrichment analysis on signaling pathways was performed by Cytoscape. The potential biological functions of targets were verified by immunohistochemistry and Western blot assay. The results showed that KXS significantly improved the behavioral indexes. There were 64, 91, and 44 potential targets of KXS identified in cortex, thalamus, and hippocampus, respectively, according to the target identification experiment. The functions of these targets were mainly associated with vasopressin-regulated water reabsorption, salmonella infection, thyroid hormone synthesis, and other signaling pathways. Besides, the results of immunohistochemistry and Western blot showed that KXS up-regulated the expressions of argipressine(AVP) in the cortex, heat shock protein 60(HSP60), cytochrome C oxidase 4(COX4), and thyrotropin-releasing hormone(TRH) in the thalamus, and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and nuclear factor kappa B(NF-κB) p65 in the thalamus. Therefore, KXS may exert anti-depression effect through regulating vasopressin signaling pathway in the cortex and inflammation, energy metabolism, and thyroid hormone signaling pathways in the thalamus, and the effect of KXS on hippocampus is not significant.
Animals ; Mice ; Chromatography, Liquid ; Disease Models, Animal ; Drugs, Chinese Herbal/chemistry* ; Hippocampus ; Stress, Psychological/drug therapy* ; Tandem Mass Spectrometry ; Depression/drug therapy*