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Primary biliary cholangitis （PBC） is a chronic autoimmune disease of cholestasis in which immune factors lead to progressive small bile duct destruction， cholestasis， and eventually liver fibrosis， liver cirrhosis， and even liver failure. Macrophages， as a group with functional heterogeneity， play different roles in the whole disease process of PBC. This article summarizes the possible ways by which macrophages are involved in the pathogenesis of PBC and discusses their impact on the disease and the potential therapeutic targets of macrophages. It is pointed out that macrophages are mainly involved in innate immunity in PBC injury and are associated with gut microbiota dysbiosis， and they are also associated with cholestasis， liver fibrosis， and liver cirrhosis in the later stages of the disease.
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Acute pancreatitis-associated ascites fluid (PAAF) is a common complication in patients with acute pancreatitis (AP) and is closely associated with the severity of AP, the development of local and systemic complications, and prognosis. PAAF may originate from the leakage of abdominal blood vessels, lymphatic vessels, and pancreatic duct. Recent studies have found that early removal of PAAF by abdominal paracentesis drainage can help to reduce systemic inflammation and alleviate pancreatitis-associated organ injury, thereby improving the conditions of patients with severe AP and reducing mortality. However, it is still not completely clear how PAAF aggravates systemic inflammatory response, participates in pancreatic injury and damage of distal organs, and leads to the aggravation of disease conditions in patients with AP. Therefore, this article gives an overview of PAAF and summarizes related studies in recent years, so as to provide directions for exploring the pathophysiological process and treatment of AP.
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Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world, and it seriously harms human health. Recent studies have found that bone morphogenetic protein 4 (BMP4) might be associated with NAFLD. This article reviews the latest advances in the research on the association between BMP4 and NAFLD in China and globally and explores the potential mechanism of action of BMP4 on NAFLD, in order to provide new ideas for the prevention and treatment of NAFLD.
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Amyloid protein （AP） is used to describe the fibrous aggregates that form when proteins are misfolded， and it is associated with a series of amyloidosis diseases. When AP is deposited in the liver， it will lead to liver amyloidosis， thereby inducing related pathological changes that affect the normal physiological function of the liver； however， this disease is rarely reported and often neglected in clinical practice. This article reviews the physiological and pathological effects and mechanisms of AP in the liver， so as to improve the understanding of AP-related diseases and provide a reference for related research and clinical treatment.
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Objective:To analyze and summarize clinical and pathological characteristics of clear cell papulosis (CCP) .Methods:Clinical data were collected from 57 children with CCP, who were diagnosed in Department of Dermatology, Children′s Hospital of Chongqing Medical University from November 2014 to March 2022, and their clinical and pathological characteristics were analyzed.Results:Among the 57 patients, 30 were males and 27 were females; their age ranged from 6 months to 7 years and 10 months; the age at onset ranged from 1 to 74 months, and 39 (68.4%) experienced onset of disease in infancy; the course of disease ranged from 1 to 84 months. Skin lesions mainly manifested as millet- to soybean-sized roundish white macules or short bar-like white macules measuring 1 - 2 cm in length. Most patients (49 cases, 85.9%) had skin lesions less than 20 in number. The most common location of skin lesions was the lower abdomen (35 cases, 61.4%), followed in turn by chest or upper abdomen (34 cases, 59.6%), anterior axilla or armpit (17 cases, 29.8%), and vulva (11 cases, 19.3%). Short bar-like white macules predominated on the chest or upper abdomen (23/34, 65.7%) and anterior axilla or armpit (10/17), roundish white macules predominated on the lower abdomen (30/35, 85.7%), and the vulvar lesions all manifested as roundish white macules. Histopathological findings showed that slightly larger cells with abundant clear cytoplasm were scattered in or above the basal layer of the epidermis, and these cells were positive for cytokeratin 7, carcinoembryonic antigen, and periodic acid-Schiff staining.Conclusion:CCP mainly occurred in young children, roundish white macules predominated on the lower abdomen and vulva, and short bar-like white macules predominated on the chest or upper abdomen, as well as on the anterior axilla or armpit, indicating that CCP has strongly identifiable clinical features.
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Objective:To analyze 141 cases clinically misdiagnosed as melanoma, and to improve the understanding and diagnosis of diseases.Methods:Totally, 141 cases preliminarily diagnosed as melanoma, which was finally excluded according to histopathological examination results, were collected from the pathological database of Department of Dermatology, Xijing Hospital, The Fourth Military Medical University from November 2001 to September 2019, and their clinical and histopathological data were analyzed retrospectively.Results:Among the 141 cases clinically misdiagnosed as melanoma, 64 were males and 77 were females. Their median age at the time of misdiagnosis was 51 years, and the average disease duration was 103.4 months. The patients mainly presented with patches and papules, most of which were black in color. Based on histopathological manifestations, 35 patients were diagnosed with pigmented nevi, 29 with basal cell carcinoma, 15 with seborrheic keratosis, 7 with Bowen′s disease, 6 with nail melanin spots, 5 with epidermal cysts, 4 with poroma, 4 with hemorrhage, 4 with dermatofibroma, and 23 with other skin diseases.Conclusions:In clinical practice, some diseases with characteristics of melanoma are liable to be misdiagnosed. It is necessary to grasp their clinical features and actively carry out auxiliary examinations such as dermoscopy and histopathological examinations to confirm the diagnosis and reduce the misdiagnosis rate.
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Connective tissue nevi (CTN) , a kind of benign skin hamartomas, can be classified into 3 types according to the excessive components predominating in skin lesions, including collagen type, elastin type and proteoglycan type, and each type of CTN includes various inherited and acquired diseases. Therefore, genetic, clinical, and histopathological features should be considered for the confirmation of diagnosis of CTN and its subtypes. According to the latest Chinese and international literature, this review elaborates clinical classification and histopathological characteristics of CTN, aiming to further strengthen the understanding of this disease.
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As a novel star molecule, gasdermin D (GSDMD) plays an important role in the amplification of immune inflammatory response and the process of pyroptosis. After being cleaved and activated by caspase-1, the N-terminal of GSDMD is rapidly released, which anchors on the cell membrane and forms pores, thereby leading to pyroptosis, accompanied by the release of a large amount of the strong proinflammatory factors IL-1β and IL-18. Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, liver failure, and hepatocellular carcinoma. This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases. In addition, it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.
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Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.
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Exosomes (EXOs) are formed by intracellular multivesicular bodies and carry a variety of biomacromolecules such as lipids, proteins, encoding and non-coding RNAs, and mitochondrial DNA. EXOs can be released in vivo by different cell types, including hepatocytes, hepatic stellate cells, and immune cells and play the role of intercellular communication. More and more studies have shown that EXOs are involved in the development, progression, and prognosis of chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection and are expected to become potential biomarkers for the early diagnosis and prognostic evaluation of HBV-related HCC. This article reviews the role of EXOs in the host infection process of HBV and the importance of EXOs in the development, progression, and prognosis of CHB and HCC, in order to provide new ideas for the basic and clinical research in this field.
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Sulforaphane is a phytochemical with a variety of biological activities that exists widely in Cruciferae plants. This article summarizes the recent experimental studies of sulforaphane in the treatment of various types of liver injury in China and globally and reviews the role and mechanism of sulforaphane in protecting against liver injury. Based on the experimental animal models of liver injury, this article summarizes the therapeutic effect of sulforaphane on the models of chemical liver injury, drug-induced liver injury, alcoholic liver injury, immunological liver injury, and ischemia/reperfusion liver injury and analyzes the mechanism of action of sulforaphane in improving experimental liver injury, so as to provide a reference for in-depth research on sulforaphane in protecting against liver injury.
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The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year, with limited treatment methods, and its pathogenesis is a research hotspot at present. In order to better clarify its pathogenesis, it is urgent to develop advanced, safe, and effective in vitro or in vivo models to understand and develop treatment strategies for this disease. This article reviews the in vitro models commonly used in the preclinical study of NAFLD and discusses their advantages and disadvantages, so as to provide a theoretical basis for the pathogenesis and treatment of NAFLD.
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Liver cirrhosis is a liver disease caused by various factors and is characterized by diffuse fibrous hyperplasia, lobular structural damage, and pseudolobule formation. Bile duct proliferation has been observed in a variety of animal models of liver cirrhosis and patients with liver cirrhosis caused by different etiologies, and it is regulated by signaling pathways with the involvement of multiple regulatory factors such as neuropeptides, neurotransmitters, and hormones. Moreover, the proliferated bile ducts promote the formation of liver fibrosis by mediating the proliferation and activation of hepatic stellate cells. This article summarizes the changes of the intrahepatic bile duct system in liver cirrhosis and its influence on the process of liver fibrosis, various signaling pathways associated with cholangiocyte proliferation and liver fibrosis, and the value of the dynamic evolution of bile duct structure in predicting the degree of liver fibrosis. It is pointed out that bile duct proliferation may become a potential target for the intervention of liver fibrosis, which provides new ideas and methods for early treatment and reversal of liver fibrosis.
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The pathogenesis of rosacea has not been fully elucidated. It is currently believed that genetic factors, local skin immune imbalance, neuroimmune and neurovascular dysfunction, skin barrier function abnormalities, microbiota imbalance, etc., are all involved in the occurrence and development of rosacea. This review summarizes research progress in the pathophysiological pathogenesis of rosacea.
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Objective:To analyze clinical and pathological features of childhood perforating pilomatricoma, and to explore its pathogenesis.Methods:A retrospective analysis was conducted on clinical and histopathological data from 29 children with perforating pilomatricoma in Department of Dermatology, Beijing Children′s Hospital from 2014 to 2020.Results:Among the 29 patients, 11 were males, and 18 were females, with a male-to-female ratio of 1∶1.64. Their age at onset ranged from 3 months to 14 years and 10 months, and the median age at onset was 4.58 years. The disease duration ranged from 2 months to 2 years, with an average of 8.72 months. The perforation occurred 2 days to 1 year and 6 months after the onset of pilomatricoma, with an average of 1.85 months. Ulceration occurred in 1 patient after the treatment with ichthammol, as well as in 3 patients after local scratching or bumping, and spontaneous ulceration without definite precipitating factors occurred in the remaining 25 patients. The average duration from the onset of disease to tumor perforation was 6.87 months. Skin lesions occurred on the face in 15 cases, on the lateral neck in 8, on the upper limb in 4, as well as on the scalp in 2. Perforating pilomatricoma clinically manifested as indurated subcutaneous nodules with crusts or ulcers, and was classified into 3 subtypes: ulcerative type (19 cases) , horny type (8 cases) , and crusted type (2 cases) . The tumor diameter ranged from 0.3 to 2.5 cm, with an average of 1.2 cm. Histopathological examination showed that the tumor was located in the superficial to middle dermis, and mainly consisted of basophils and ghost cells; in 19 cases, the tumor mass was extruded onto the skin surface through a perforated epidermal channel, and the epidermis around the perforation site was hyperplastic and invaginated into the dermis, forming epithelial tunnels surrounding the tumor; in 4 cases, the skin on the tumor surface was thinned and ruptured; in 6 cases, the perforation site could not be observed due to surgical separation of the epidermis and tumor. All lesions were resected, and no infection or recurrence was observed during the postoperative follow-up.Conclusions:Childhood perforating pilomatricoma mostly occurs on the face and neck, usually with rapid progress, and can be classified into ulcerative type, horny type and crusted type. Histological findings suggest that transepithelial elimination is an important mechanism underlying the occurrence of perforation in pilomatricoma.
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Objective:To investigate clinicopathological features of hypopigmented mycosis fungoides (HMF) and hypopigmented interface T-cell dyscrasia (HITCD) .Methods:A total of 41 patients with cutaneous hypopigmented lymphoproliferative diseases, who had complete clinicopathological data, were collected from Department of Dermatology, the Third People′s Hospital of Hangzhou from January 2015 to September 2020, and the clinicopathological and immunophenotypic features were analyzed. Comparisons of normally distributed measurement data were carried out using t test, comparisons of categorical data using Chi-square test or Fisher′s exact test, and comparisons of ranked data between 2 groups using rank-sum test. Results:All of the 41 patients clinically presented with irregular hypopigmentation, some of which was accompanied by erythema or furfuraceous scales. In terms of pathological features, 21 patients showed infiltration and aggregation of atypical lymphoid cells in the epidermis, which was consistent with typical pathological features of mycosis fungoides, and they were diagnosed with HMF; 20 patients showed vacuolar degeneration of the basal layer, accompanied by infiltration of lymphoid cells and mild epidermotropism, and they were diagnosed with HITCD. All immune cells expressed T-cell phenotype, and epidermal lymphocytes expressed a CD8-dominated phenotype in 14 (67%) cases of HMF and 13 (65%) of HITCD. In the epidermis, the total number of lymphocytes was significantly higher in the HMF group than in the HITCD group ( t= 1.81, P= 0.012) ; in the dermis, the number of CD4 + lymphocytes and CD8 + lymphocytes, and the total number of lymphocytes were all significantly higher in the HMF group than in the HITCD group ( t= 2.64, 1.51, 2.60, P= 0.012, 0.002, 0.001, respectively) . All patients were treated with narrow-band ultraviolet B radiation. Among 34 patients who completed the follow-up, 30 achieved complete clearance of skin lesions without recurrence, including all patients with HITCD, and 4 with HMF achieved partial regression of the lesions. Conclusions:Compared with HMF, HITCD presents different pathological characteristics and benign biological behaviors. Thus, HITCD should be distinguished from HMF as an independent disease. Phototherapy alone is effective for the treatment of HITCD.
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Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.
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The incidence and mortality rates of cholangiocarcinoma (CCA) are increasing constantly, and it is of great importance to explore new therapeutic targets. Ferroptosis, a unique pattern of cell death caused by iron-dependent cellular oxidative injury, is closely associated with iron metabolism and oxidative stress imbalance in cancer and has become a research hotspot in the field of tumor. This article introduces the mechanism of ferroptosis and the research advances in ferroptosis involved in the development and progression of CCA, and it is pointed out that the regulatory mechanism of ferroptosis has an important clinical value in the malignant progression of CCA.
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Particulate matter 2.5 (PM2.5), as one of the main components of atmospheric particulate matter, has become an important factor affecting people's health; however, there are relatively few studies on the association of PM2.5 with the development and progression of liver cancer. This article reviews the epidemiological study of PM2.5 and liver cancer, summarizes the mechanisms of PM2.5 causing liver cancer (including changing enzyme activity, affecting gene expression, inducing endoplasmic mesh stress, causing liver fat degeneration, and leading to liver fibrosis), and discusses the influence of PM2.5 exposure on the prognosis of liver cancer.
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Objective To investigate the effect of Yipi Yanggan prescription on the malignant transformation of liver stem cells in liver precancerous lesion induced by diethylnitrosamine (DEN) and its possible molecular mechanism. Methods A total of 35 male Sprague-Dawley rats were randomly divided into normal control group (blank group), DEN model group (model group), DEN+Yipi Yanggan prescription group (Yipi Yanggan prescription group), and DEN+Hugan tablet group (Hugan tablet group), with 5 rats in the blank group and 10 rats in the other three groups. Intraperitoneal injection of DEN was performed to establish a model of liver precancerous lesion, the rats were sacrificed after 16 weeks of administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb) were measured; liver tissue was collected to observe the changes in size and appearance and calculate liver weight ratio (liver index); HE staining and Sirius Red staining were used to observe the pathological and morphological changes of rat liver tissue; immunohistochemistry was used to measure the expression of OV6 and glutathione S-transferase-Pi (GST-Pi); RT-PCR was used to measure the mRNA expression of EpCAM, CD133, and CD90, and Western blot was used to measure the protein expression of PI3K, Akt, and mTOR and their phosphorylation level. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the model group, the Yipi Yanggan prescription group and the Hugan tablet group had significant improvements in liver pathology and morphology, significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Compared with the Hugan tablet group, the Yipi Yanggan prescription group showed a more significant protective effect on the liver, with significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Conclusion Yipi Yanggan prescription can improve liver precancerous lesion induced by DEN in rats by inhibiting the malignant transformation of liver stem cells, and its mechanism of action may be associated with the PI3K/Akt/mTOR signaling pathway.