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Mitophagy is a type of selective autophagy during which cells specifically remove damaged mitochondria in response to nutrient deficiency or external stimulation and thus maintain the integrity of mitochondrial function and cellular homeostasis. In recent years， a large number of studies have shown that dysfunction of mitophagy is closely associated with the development and progression of various liver-related diseases such as nonalcoholic fatty liver disease， drug-related liver injury， viral hepatitis， and hepatocellular carcinoma. This article summarizes the specific mechanisms of mitophagy in regulating liver-related diseases and further elaborates on the potential therapeutic targets of mitophagy in liver-related diseases， in order to provide more effective therapeutic strategies for the clinical treatment of liver diseases.
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Drug-induced liver injury is caused by the drug itself and/or its metabolites during drug use or occurs due to hypersensitivity or reduced tolerance to the drug in a particular body type. In the last three years of the diagnosis and treatment of coronavirus disease 2019 （COVID-19）， antiviral drugs have played a very important role， but there are many reports on liver injury caused by anti-COVID-19 drugs in China and globally， with unknown pathogenesis of liver injury caused by such drugs. This article reviews the research advances in the types of antiviral drugs for COVID-19 and their mechanism in inducing liver injury， in order to promote the rational use of antiviral drugs.
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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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Liver failure often has rapid progression， multiple complications， and dangerous conditions. Acute pancreatitis is a common comorbidity during the progression of liver failure， and since acute pancreatitis has extremely similar clinical symptoms and signs to liver failure complicated by spontaneous peritonitis， it is often neglected in clinical practice. This article elaborates on the mechanisms of liver failure complicated by acute pancreatitis from the five aspects of inflammatory response， duodenal papillary dysfunction， gut microbiota dysbiosis， oxidative stress， and microcirculatory disturbance and proposes corresponding preventive measures based on these mechanisms.
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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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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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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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Objective:To analyze skin manifestations of pediatric inflammatory bowel disease (IBD) .Methods:Children with IBD were collected from pediatric wards in Peking University Third Hospital from January 2010 to January 2022, and their skin manifestations were retrospectively analyzed.Results:A total of 50 children with IBD were included, including 27 with Crohn′s disease and 23 with ulcerative colitis. Twenty-five (50%) patients had skin manifestations, including specific skin manifestations in 11 (22%) and relevant skin manifestations in 11 (22%) . Specific skin manifestations included cutaneous perianal Crohn′s disease in 2 cases, and anal fistula and/or perianal abscess in 9 cases; relevant skin manifestations included erythema nodosum in 5 cases, aphthous stomatitis in 3 cases, psoriasis in 1 case, polyarteritis nodosa in 1 case, and Henoch-Sch?nlein purpura in 1 case. Compared with the ulcerative colitis group, the Crohn′s disease group was more prone to suffer from specific skin manifestations and relevant skin manifestations, and there were significant differences in the prevalence of specific and relevant skin manifestations between the two groups (both P < 0.05) . Of the 27 children with Crohn′s disease, 19 (70%) had one or more skin manifestations, 2 of whom successively presented with 4 different skin manifestations. One child with Crohn′s disease and 1 with ulcerative colitis had 3 different skin manifestations in different periods. The fecal calprotectin level was elevated in all children with skin manifestations, and in 12 (48%) children without skin manifestations. The skin lesions of 5 children were improved or subsided after dose adjustment (1 case) or switch (4 cases) of biological agents. Conclusions:Half of the children with IBD have skin manifestations, and children with Crohn′s disease are more prone to have specific and relevant skin manifestations. Different skin manifestations could be observed in the same child in different periods. Multidisciplinary teamwork is conducive to the overall control of this disease.
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Objective:To analyze clinical and pathological features of follicular porokeratosis.Methods:Clinical and histopathological data were collected from 8 patients who were diagnosed with follicular porokeratosis in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2015 to February 2022, and analyzed retrospectively.Results:Among the 8 patients, 6 were males and 2 were females. Their average age at onset was 36 years (range, 6 - 67 years) , and the average duration from onset to diagnosis was 6 years (range, 0.5 - 20 years) . No obvious precipitating factors were found. The patients presented with multiple or solitary, small (diameter < 1 cm) , round, long-standing stable reddish-brown maculopapules or plaques with few or no scales on their surface. Most patients had no subjective symptoms, but for some occasional mild itching sensation. Dermoscopic examination of 4 patients showed that keratotic plugs were all present at the opening of hair follicles. Histopathological manifestations of the 8 skin lesions were similar: roughly normal epidermal thickness or mildly irregular acanthosis, parakeratotic columns only at the infundibulum of hair follicles, and thinner or disappeared granular layer containing some dyskeratotic cells. Of the 8 patients, 6 were treated with surgical excision, topical drugs, or laser cautery, etc. The follow-up results showed that surgical excision could cure the primary skin lesions, but could not prevent new skin lesions, and other treatments were basically ineffective.Conclusions:Follicular porokeratosis, a special type of porokeratosis, mostly occurs on the facial area of middle-aged males. This disease usually progresses slowly, and is histopathologically characterized by unique parakeratotic columns only present at the opening of hair follicles. The diagnosis of follicular porokeratosis should rely on both clinical manifestations and histopathological findings.
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Objective:To investigate dermoscopic features of childhood vulvar lichen sclerosus.Methods:From January 2019 to May 2021, 79 female children with vulvar lichen sclerosus were collected from Kunming Children′s Hospital, and their dermoscopic features at first and return visits were analyzed retrospectively.Results:Among the 79 female children with vulvar lichen sclerosus, their age ranged from 2.4 to 12 years, the age at onset was 5.6 ± 2.12 years, the course of disease was 14.23 ± 12.36 months, and 30 children received regular follow-up and treatment. Among 329 skin lesions at the first visit, characteristic vascular shapes were observed in 149 (45.3%) , including linear vessels in 129, punctate vessels in 25, coiled vessels in 19, and hairpin-like vessels in 12; degenerative structures and pigment abnormalities were seen in 207 (62.92%) , including bluish-gray pigmented structures in 136, brown pigmented structures in 51, pepper-like patterns in 15, etc.; yellowish-white structureless areas were found in 280 (85.1%) , follicular keratotic plugs in 97 (29.5%) , and reddish-violet globules and patches in 66 (20%) . Among 238 skin lesions at the return visit, characteristic vascular shapes were observed in 100 (42%) , including linear vessels in 87, dendritic vessels in 21 and punctate vessels in 4, and no hairpin-like vessels were observed; degenerative structures and pigment abnormalities were seen in 154 (64.70%) , including brown pigmented structures in 93, bluish-gray pigmented structures in 57, and pepper-like patterns in 4; yellowish-white structureless areas were found in 165 (69.3%) , follicular keratotic plugs in 62 (26.1%) , and reddish-violet globules and patches in 8 (3.4%) . The prevalence rates of bluish-gray pigmented structures, yellowish-white structureless areas, reddish-violet globules and patches, punctate vessels, hairpin-like vessels, and coiled vessels in the skin lesions were all significantly lower at the return visit than at the first visit (all P < 0.05) , while the prevalence rate of the brown pigmented structure was significantly higher at the return visit than at the first visit ( P < 0.05) . Conclusion:Under a dermoscope, yellowish-white structureless areas are a highly specific characteristic of childhood vulvar lichen sclerosus, and therapeutic effect can be monitored by observing changes in dermoscopic features, including brown pigmented structures, bluish-gray pigmented structures, yellowish-white structureless areas, reddish-violet globules and patches, and vascular structures. Dermoscopy shows favorable application value in auxiliary diagnosis and follow-up observation of childhood vulvar lichen sclerosus.
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Objective:To investigate clinicopathological features of swimming pool granuloma.Methods:From January 2018 to January 2021, 56 patients with swimming pool granuloma were collected from Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, and their clinical and pathological characteristics were retrospectively analyzed.Results:Among the 56 patients, 16 were males and 40 were females, with an average age of 60.84 years. The most common exposure type among these patients was handling of infected fishes or seafood by aquaculture workers and residents in daily cooking (31/56) , the average incubation period was 4.58 weeks, and the average time to diagnosis was 3.19 months. All skin lesions were located at the upper extremities, mainly manifesting as erythema and papular nodules, and sometimes as pustules, ulcers, granulomas or verrucous plaques. Eleven patients presented with solitary skin lesions, 36 with sporotrichoid skin lesions, and 6 with bilateral sporotrichoid lesions. Histopathologically, infectious granulomas were observed in all patients except 4 without specific changes, and 37 presented with characteristic exudative necrosis, with varying amounts of fibrinoid exudative or necrotic elements in the center, and a large number of neutrophils, histiocytes and multinucleated giant cells infiltrating inside or around it. Sequences of Mycobacterium marinum were identified in all 56 cases by metagenomic DNA sequencing of pathogenic microorganisms. Conclusion:In Tianjin area, swimming pool granuloma mostly affected elderly females, handling of infected fishes or seafood was the main type of exposure, and skin lesions were histopathologically characterized by exudative necrotic granulomas.
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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.