1.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
2.Targeted therapeutic strategies for melanoma.
Shiwei ZHANG ; Ruxin XIE ; Ai ZHONG ; Junjie CHEN
Chinese Medical Journal 2023;136(24):2923-2930
Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.
Humans
;
United States
;
Melanoma/genetics*
;
Skin Neoplasms/pathology*
;
Mutation
;
Proto-Oncogene Proteins B-raf/therapeutic use*
3.Stevens-Johnson syndrome secondary to massive inflammatory hyperplasia of bilateral lingual margins: a case report and literature review.
Juan LIN ; Fan YU ; Xiaona LI ; Bingyan LI ; Ruipu ZHANG ; Weihong XIE
West China Journal of Stomatology 2023;41(5):599-603
Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.
Male
;
Humans
;
Stevens-Johnson Syndrome/drug therapy*
;
Hyperplasia/pathology*
;
Skin
;
Drug Hypersensitivity/pathology*
;
Tongue
4.Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans: a clinicopathological and genetic analysis.
Min CHEN ; Yu Mei CHEN ; Yang LU ; Xin HE ; Heng PENG ; Hong Ying ZHANG
Chinese Journal of Pathology 2023;52(1):13-18
Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.
Female
;
Humans
;
Male
;
Collagen Type I, alpha 1 Chain
;
Dermatofibrosarcoma/pathology*
;
In Situ Hybridization, Fluorescence
;
Oncogene Proteins, Fusion/genetics*
;
Proto-Oncogene Proteins c-sis/genetics*
;
Skin Neoplasms/pathology*
;
Adult
6.Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm.
Xiao-Li ZHANG ; Bing LIU ; Nan LI ; Lu-Ke LI ; Xuan-Jing JI ; Xue-Fang ZHOU ; Min-Fang WANG ; Hui-Li XU
Journal of Experimental Hematology 2023;31(1):254-260
OBJECTIVE:
To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).
METHODS:
The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.
RESULTS:
4 patients had bone marrow, spleen and lymph nodes involvement, 2 patients had skin lesions, and 3 patients had central nervous system infiltration. Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients, and CD304 in 3 patients. One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again. One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.
CONCLUSION
The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.
Humans
;
Dendritic Cells
;
Retrospective Studies
;
Skin Neoplasms/pathology*
;
Antineoplastic Agents/therapeutic use*
;
Bone Marrow/pathology*
;
Myeloproliferative Disorders
;
Hematologic Neoplasms/drug therapy*
7.Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Zhibing FU ; Yajie XIE ; Liyue ZENG ; Lihua GAO ; Xiaochun YU ; Lina TAN ; Lu ZHOU ; Jinrong ZENG ; Jianyun LU
Journal of Central South University(Medical Sciences) 2023;48(1):1-14
OBJECTIVES:
Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms.
METHODS:
Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions.
RESULTS:
Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05).
CONCLUSIONS
Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals
;
Mice
;
Dinitrochlorobenzene/metabolism*
;
Skin/metabolism*
;
Cytokines/metabolism*
;
Interleukin-17/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Dermatitis, Allergic Contact/pathology*
;
Dermatitis, Atopic/chemically induced*
;
Signal Transduction
;
RNA, Messenger/metabolism*
;
Mice, Inbred BALB C
8.Blue Nevus Hidden within the Nevus of Ota.
Xing LIU ; Hui-Ying ZHENG ; Fu-Min FANG ; He-Dan YANG ; Hui DING ; Yin YANG ; Yi-Ping GE ; Tong LIN
Chinese Medical Sciences Journal 2023;38(1):70-72
A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.
Male
;
Humans
;
Child, Preschool
;
Nevus, Blue/pathology*
;
Nevus of Ota/therapy*
;
Skin/pathology*
;
Face
;
Skin Neoplasms/pathology*
9.Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm.
Ping CHENG ; Qiu-Xaing WANG ; Lan-Lan WANG ; Jun GUAN ; Ying ZHOU ; Ting ZHANG ; Fei SU ; Liu-Qing CHEN ; Yang CAO ; Hui CHENG ; Liang ZOU
Journal of Experimental Hematology 2023;31(3):896-901
OBJECTIVE:
To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).
METHODS:
Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.
RESULTS:
Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.
CONCLUSION
BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.
Humans
;
Male
;
Female
;
Adult
;
Middle Aged
;
Retrospective Studies
;
Leukemia/pathology*
;
Hematopoietic Stem Cell Transplantation
;
Prognosis
;
Myeloproliferative Disorders
;
Skin Neoplasms/pathology*
;
Acute Disease
;
Dendritic Cells
10.Analysis of 14 cases of melanosis caused by 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene.
Ye Ting MAO ; Chun Hua LU ; Ping ZHOU ; Shi Wei YIN ; Hai Ping GAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(4):299-301
14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.
Humans
;
Melanosis/pathology*
;
Pigmentation
;
Skin/pathology*

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