Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems. In clinical practice， most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease， and the etiology of such diseases may be associated with the rheumatic disease itself， medications， metabolism， viruses， or the presence of other chronic liver diseases. Immune-mediated inflammatory responses play a significant role in liver involvement （including hepatocyte injury， intrahepatic vascular lesions， and hepatic fibrosis） in rheumatic diseases. This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases， in order to enhance the understanding of this condition among specialists in related fields.

Background Dibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. Objective To investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. Methods Thirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg⁻¹ DBP exposure group (OVA+DBP), and OVA+40 mg·kg⁻¹ DBP+50 mg·kg⁻¹ 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg⁻¹ DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. Results Compared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P<0.01), the Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) cytokines in BALF (P<0.01), and the expression levels of endoplasmic reticulum stress-related proteins IRE1α, PERK and ATF-6 (P<0.01). In addition, after the 4-PBA treatment, it was found that compared with the OVA+DBP group, the expression levels of endoplasmic reticulum stress-related proteins (IRE1α, PERK and ATF-6) were down-regulated in the OVA+DBP+4-PBA group (P<0.01), the levels of cytokines (IL-4, IL-5, IL-13, and IL-17A) in BALF and T-IgE and OVA-IgE in serum were decreased (P<0.01), and airway remodeling and mucous hyperplasia were significantly alleviated. Conclusion Long-term exposure to DBP could aggravate allergic asthma by activating the endoplasmic reticulum stress pathway. This worsening effect is accompanied by the increase of immunoglobulin IgE levels and the release of Th2 and Th17 cytokines, which in turn leads to lung histopathological changes that affect lung function.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.