Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Narrow-band ultraviolet B (NB-UVB) phototherapy has been regarded as the first-line treatment of generalized vitiligo. However, NB-UVB monotherapy exhibits limited efficacy with a long course of treatment. NB-UVB phototherapy combined with other therapies can shorten the course of treatment and improve the therapeutic effect, and has become a commonly used therapeutic regimen in clinical practice. This review summarizes research progress in the combined therapies of NB-UVB with other approaches for the treatment of vitiligo, such as glucocorticoids, afamelanotide, calcineurin inhibitors, Janus kinase inhibitors, platelet-rich plasma, fractional CO 2 laser and surgical treatment, in order to provide more options for clinical treatment of vitiligo.

Objective:To investigate the expression of anaplastic lymphoma kinase (ALK), tropomyosin receptor kinase (TRK), and recombinant C-Ros oncogene 1, receptor tyrosine kinase (ROS1) in Spitz tumors, and to analyze their associations with clinical and histopathological features of Spitz tumors.Methods:Clinical and histopathological characteristics, as well as follow-up data, were collected from patients with Spitz tumors at Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to August 2023, and retrospectively analyzed. Immunohistochemical staining for ALK, pan-TRK, and ROS1 was performed on skin tissues, and associations between the expression of these kinase proteins and clinicopathological features were analyzed.Results:A total of 57 patients with Spitz tumors were collected, including 36 females and 21 males. Immunohistochemical staining showed that 30 (52.6%) patients were positive for ALK, 4 (7.0%) were positive for ROS1, only 2 (3.5%) were positive for TRK, and 21 (36.8%) were negative for the three kinase proteins. Among the 30 ALK-positive patients, the median age was 9.5 years, 21 (70.0%) were females, and 15 (50.0%) presented with lesions on the face, which mainly manifested as papules or nodules; histologically, 29 (96.7%) patients had hypopigmented tumors with an exophytic growth pattern, and the tumor cells were mainly large and long spindle cells arranged in long cord-like, plexiform or fascicular patterns. Among the 4 ROS1-positive patients, there were 3 females and 1 male, presenting with exophytic papules or polyps; histologically, tumor cells were mostly arranged in small nests, without obvious clefts around cell nests. Two TRK-positive patients were both males aged 20 and 50 years respectively, and presented with brown and skin-colored flat papules, respectively; histologically, the tumors were located superficially with a flat base, and tumor cells spread in a pagetoid pattern in the epidermis, with some epithelioid cells and small cell nests. Among the 21 patients negative for the 3 kinase proteins, 9 were males and 12 were females, and they clinically presented with macules, papules and polypoid lesions; histologically, most tumors were located superficially, consisting of a mixture of epithelioid cells and spindle cells, with rare cytological atypia and mitotic figures, and 2 cases showed mild tissue structural and cellular atypia. Fifty-seven patients were followed up for 2 - 83.3 months, with a median follow-up of 19.2 months. Only 1 ALK-positive child experienced a recurrence, and no recurrence or lymph node metastasis was observed in the other cases.Conclusions:Among the three kinase proteins, ALK showed the highest positive rate in Spitz tumors in this study, while TRK- and ROS1-positive cases were sporadic. Histopathologically, ALK-positive Spitz tumor cells were mainly long spindle cells arranged in long cord-like or plexiform patterns, while TRK- and ROS1-positive Spitz tumors tended to have small cell nests. Both the kinase protein-positive and -negative Spitz tumors mostly had a good prognosis.

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.

Objective:To correlate serum homocysteine (Hcy) level with psychiatric symptoms and social ability in patients with schizophrenia.Methods:A total of 143 patients with schizophrenia who received treatment in the Third Hospital of Quzhou from January 2018 to January 2020 were included in this study. They were randomly divided into abnormal Hcy group (Hcy ≥ 10) μmol/L, n = 46) and normal Hcy group (Hcy < 10 μmol/L, n = 97) according to different serum Hcy levels. Baseline data, the scores of the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and the Substance Dependence Severity Scale (SDSS) were compared between the two groups. The correlation between serum Hcy level and psychiatric symptoms and social ability was analyzed using the Pearson correlation analysis. Results:PANSS total score and BPRS total score were (77.86 ± 8.37) points and (94.47 ± 9.36) points, respectively in the abnormal Hcy group, and (74.37 ± 7.94) points and (90.35 ± 9.26) points, respectively in the normal Hcy group. There were significant differences in PANSS total score and BPRS total score between the two groups ( t = 2.41, 2.47, both P < 0.05). SDSS total score was significantly higher in the abnormal Hcy group than in the normal Hcy group [(11.75 ± 2.38) points vs. (10.53 ± 2.28) points, t = 2.88, P < 0.05]. Pearson correlation analysis showed that serum Hcy level was positively correlated with PANSS positive subscale score ( r = 0.73, P < 0.001), general mental symptom score ( r = 0.43, P = 0.032) and PANSS total score ( r = 0.53, P = 0.027), but it was not correlated with PANSS negative symptom score ( P > 0.05). Serum Hcy level was positively correlated with BPRS excitement subscale score ( r = 0.42, P = 0.037) and hostility subscale score ( r = 0.37, P = 0.047), but it was not correlated with anxiety, blunted affect, unusual thought content subscale scores and BPRS total score (all P > 0.05). Conclusion:Serum Hcy level is correlated with psychiatric symptoms and social ability in patients with schizophrenia. The higher the level of Hcy, the more severe the psychiatric symptoms, and the higher the degree of social disability.

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.

Objective:To investigate clinical and histopathological features of mucinous nevi.Methods:Clinical and pathological data were collected from 10 patients with clinically and histopathologically confirmed mucinous nevi in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2014 to December 2019, and retrospectively analyzed.Results:All cases developed mucinous nevi in childhood, with an average age of onset being 6.5 years. Of the 10 patients, 7 had lesions on the trunk, among whom 4 had lesions on the back; the remaining 2 had lesions on the limbs, and 1 had generalized lesions on the trunk and limbs. The skin lesions were locally arranged in lines, bands or clusters, and skin-colored, reddish or yellow in color, with the texture varying from soft to hard. Histopathological examination showed that 10 patients presented with disordered arrangement of collagen fiber bundles in the dermis and mucin deposition at varying locations and to different degrees among them, 6 with thickened and red-stained collagen fibers in the deposition area, and the remaining 4 with sparse and decreased collagen; focal liquefaction degeneration of the basal layer was observed in 2 cases, and different amounts of mature adipose tissue in the dermis were seen in 3 cases.Conclusions:Mucinous nevus pathologically manifests as mucin deposition of varying degrees among disorderedly arrangd collagen fiber bundles in the dermis, which is similar to some other diseases, and is easily misdiagnosed. Close combination of clinical and pathological features facilitates confirmed diagnosis.

Objective: To analyze clinical and pathological features of papular elastorrhexis. Methods: Clinical data were collected from 22 patients with confirmed papular elastorrhexis in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Pekin Union Medical College from September 2006 to May 2018. Clinical manifestations, pathological findings and follow-up results were retrospectively analyzed. Results: The average age of onset of the 22 patients was 5.7 years (range: 1 - 10 years) , and the male to female ratio was 4.5∶1. The average duration from the occurrence of disease to the confirmation of diagnosis was 1.5 years, and no definite etiology was found. The patients had no itching or pain sensation. Skin lesions were soft, slightly elevated, well-circumscribed, round, oval or polygonal-shaped, white papules with diameters of 1 - 10 mm, and wrinkles appeared on the surface of the papule when the papule was pushed towards its center. Among the 22 patients, 16 (73%) presented with scattered lesions, 13 (59%) had less than 5 papules, and lesions were located in the trunk in 21 (95%) . Histopathological examination of skin lesions in 8 patients showed no obvious increase of collagen fibers in the superficial and middle dermis, which were normally arranged with slightly widened spaces between them. Elastic fiber staining showed that elastic fibers disappeared or were dissociated focally in the superficial and middle dermis. After confirmed diagnosis, the 22 patients received no treatment. In 18 patients, skin lesions did not continue to expand after onset, and no new skin lesions occurred. Skin lesions were slightly enlarged, but remained steady thereafter in 4 patients. Sixteen patients achieved partial remission. Conclusions Papular elastorrhexis is a rare skin disorder of elastic fibers that occurs predominantly during childhood and adolescence, and its diagnosis relies on clinical manifestations combined with histopathological findings. No special treatment is needed and the prognosis is good.

Transmembrane proteins (TMEMs) are a class of membrane proteins, also known as integral membrane proteins, that contain at least one transmembrane structure. A variety of membrane protein function has been found closely related to the proliferation, invasion and metastasis of malignant tumors: TMEM48, TMEM45A/B, TMEM14A, TMEM158 and TMEM206 have tumor promoting effects; TMEM25 and TMEM7 have antitumor effects; TMEM16A, TMEM17, TMEM97, TMEM88 and TMEM176 play heterogeneity roles in different tumors. These TMEMs can be used as potential prognostic indicators and new therapeutic targets.