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.

Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95％confidence interval[CI]:0.2—1.0),STE(OR=1.5,95％CI:1.0—2.1),and PIIIP(OR=1.1,95％CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34％and a sensitivity of 96.36％,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.

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.

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 explore the role and significance of nucleic acid testing(NAT) in blood transfusion. 【Methods】 The NAT data from March 2015 to December 2019 were collected and analyzed by inquiring the monthly analysis table of NAT-yielding results and the information management system of Qiao Blood Station (shinow9.5). The NAT capability of Kehua and Roche nucleic acid screening systems were compared. 【Results】 A total of 19 8348 samples were screened by Kehua and Roche nucleic acid screening systems, 67 reactive samples were detected, including 65 HBV DNA reactive samples, 2 HIV RNA reactive samples, and no HCV RNA reactive sample. 151 096 samples and 47 252 samples were detected by Kehua system and Roche system, with the resolution ratio at 44.55% vs 56.25% (P>0.05) and the reactive rate at 0.032% vs 0.038 % (P>0.05), respectively. The effective resolution ratio were 42.86%, 45.45%, 50%, 40% and 57.14% each year from 2015 to 2019, and the reactive rates were 0.041%, 0.042%, 0.027%, 0.021% and 0.038%, respectively. There was no statistical significance among each year by the effective resolution ratio and the reactive rate (P>0.05). The reactive yield at resolution was the highest (77.42%, 24/31) in minipool with CT <33 and the lowest(13.64%, 3/22) in minipool with CT≥40, mostly(73.13%, 49/67) remaining in CT<35. 【Conclusion】 Both Kehua and Roche screening system can detect NAT reactive samples in enzymatic non-reactive samples. The lower the CT value of mini pool, the greater the resolution probability of reactive samples. NAT can further guarantee the safety of blood transfusion.

Objective To understand the epidemic characteristics of different virus types of hand, foot and mouth disease (HFMD) in Zhaotong City, and provide guidance and recommendations for the prevention and control of HFMD, and to analyze seasonal characteristics of different virus types of HFMD in Zhaotong City. Methods The epidemiological characteristics of different virus types of HFMD in Zhaotong City from 2014 to 2017 were analyzed using the concentration and circular distribution methods. Results The main pathogens detected were EV71, Cox A16 and other enteroviruses, which were 216, 182, and 294, respectively, accounting for 57.45%, 73.44%, and 67.11%. M was 0.86, indicating that EV71 had strong seasonality. The Rayleigh test showed statistically significant differences (Z = 99.53, P <0.001). ā = 157 °, the peak day of onset was May 10, similar to untyped (May 16), the peak period was April 21-June 1, and the epidemic period was April 1-June 21. Conclusion According to the incubation period of hand-foot-mouth disease and the period of time during which the vaccine develops protective effects, vaccination of hand-foot-mouth disease vaccine at the peak period has a good guiding significance for the timeliness and pertinence of vaccination.

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.

Objective To discuss the diagnosis and differential diagnosis of microcystic adnexal carcinoma (MAC).Methods Totally,10 patients with MAC were enrolled from Hospital for Skin Diseases,Chinese Academy of Medical Sciences from 2003 to 2017.Their clinical manifestations,histopathological and immunohistochemical features,treatment and prognosis were retrospectively analyzed.Results Of the 10 patients,3 were males and 7 were females.Their average age at the onset of MAC was 51.65 years.Skin lesions all occurred on the face,and on the upper lip in 6 cases.The lesions usually presented as solitary plaque or nodule,and ulceration occurred in 4 cases.Histopathologically,skin lesions consisted of epithelial cords with different numbers of keratinous cysts and tubular structures,and neural involvement occurred in 6 cases.However,mitotic figures were rare.Immunohistochemical staining showed epithelial cells and keratinous cysts stained positive for cytokeratin,as well as tubular structures and glandular cavities stained positive for carcinoembryonic antigen and epithelial membrane antigen.All the patients received surgical excision,and one patient experienced in situ recurrence 13 years later.No distant metastasis occurred in these patients.Conclusions MAC mainly presents as red plaques with occasional ulceration on the upper lip.Its definite diagnosis depends on characteristic histopathological changes in bidirectional differentiation into hair follicles and sweat glands,and immunohistochemical features are helpful to distinguish MAC from other adnexal tumors.

Objective To understand the awareness level of iodine deficiency (ID) impairments and the attitude on edible iodized salt,and its consumption among doctors and nurses in cities,in order to provide scientific evidence for health education on iodine deficient disorders (IDD) in the future.Methods The questionnaire was self-designed,and spread through the web page of Wenjuanxing,an online server company,from May 6 to June 6,2017.At the end of the survey,a total of 481 valid questionnaires were reclaimed,in which ratio of gender was female 63.8％ (307/481),male 36.2％ (174/481).The data were analyzed by SPSS 22.0,including logistic regression analysis with backward according to the statistical significant level of P ＜ 0.05.Results Among doctors and nurses,90.4％ (435/481) knew ID impairments;72.8％ (350/481) answered intelligent disability as the most serious problem of ID;55.5％ (267/481)misunderstood that the areas in which they lived were not ID areas,although all cities surveyed were ID areas;41.0％ (197/481) of doctors and nurses misunderstood that coastal residents did not need to consume iodized salt.About the evaluation of iodine nutrition status of current population,15.6％ (75/481) of respondents judged as iodine excess.About consuming edible salt,76.3％ (367/481) selected iodized,9.6％ (46/481)non-iodized,and 14.1％ (68/481) both iodized and non-iodized.The results of logistic regression analysis showed the factors that prevents health care workers from choosing iodized salt were:"living in coastal areas","think him or her as iodine adequate","know that iodine deficiency can affect the development of children but still adhere to the consumption of non-iodized salt";the factors that promoted the choice of iodized salt for medical staff were "insist on buying iodized salt,and do not choose non-iodized salt",and 75.8％ (238/314)of them knew that intelligent disability as the most serious problem of ID.Conclusions Most doctors and nurses have high level of knowledge on ID and its control.But lack of information,as well as misunderstanding of "coastal areas iodine adequate" and worry about "excess iodine causes thyroid diseases and cancer",which would hinder the active consumption of iodized salt.Health education for them should be conducted through professional ways,stressing on the threaten of ID environment,sharing the information about national and local progress on control of IDD and iodized salt safety,and clarifying the relationship between iodine salt or iodine and thyroid cancer and nodules.

Objective To investigate clinical and pathological features of 6 cases of disabling pansclerotic morphea (DPM).Methods Clinical and pathological manifestations of and follow-up results in 6 patients,who were clinically and histopathologically diagnosed with DPM in the Department of Pathology,Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College from 2007 to 2017,were retrospectively analyzed.Results Among the 6 patients,4 were male and 2 were female.The age of onset ranged from 3 to 10 years,with an average age of 6.5 years.The average duration from the occurrence to the confirmation of the diagnosis was 6.2 years (range,2-10 years).At all the lesional sites,skin atrophy,thining and tightness occurred,and the limbs became thin.Additionally,there were muscular atrophy and visible deep thick veins on the surface of the limbs.The contracture,deformity and dysfunction of the adjacent joints occurred in 4 cases,and the lower limbs were obviously shortened in 2 cases.Peripheral blood examination showed no increase of eosinophils or hypergammaglobulinemia.Imaging examination revealed smooth cortical bone and clear trabecular bone,and no osseous abnormality was observed.Histopathological examination of contracted skin lesions of the lower limbs revealed atrophic and thinned epidermis,hyperpigmentation in the basal layer,hyperplastic,thickened,hardened and partly homogenized collagen fibers in the middle to deep dermis,subcutaneous adipose tissue region and deep tissue of the skin.Conclusions DPM usually does not affect viscera,but often involves deep tissue of the limbs.Histopathologically,DPM is mainly characterized by obviously hyperplastic and hardened collagen fibers in the dermis and subcutaneous tissue.