1.Cutaneous hypopigmented lymphoproliferative disorders: a clinicopathological study of 41 cases
Jiaqi WANG ; Ping WANG ; Liuyu LI ; Qimin FAN ; Mengyan ZHU ; Yanqing WANG ; Hongyu ZHOU ; Hong SHEN ; Ai′e XU
Chinese Journal of Dermatology 2022;55(2):110-115
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.
2.Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma (ESCC)
Jie CHEN ; Yan WANG ; Di ZHAO ; Lingyuan ZHANG ; Weimin ZHANG ; Jiawen FAN ; Jinting LI ; Qimin ZHAN
Acta Pharmaceutica Sinica B 2021;11(1):143-155
Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.
3.Retrospective cohort study on the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value
Qimin MA ; Xiaobin LIU ; Guosheng WU ; Wenjia HOU ; Xiaoming FAN ; Tuo SHEN ; Kang′an WANG ; Feng ZHU
Chinese Journal of Burns 2021;37(2):150-156
Objective:To study the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value.Methods:Retrospective cohort study was performed on medical records of 37 adult patients with extensively severe burn who were admitted to the First Affiliated Hospital of Naval Medical University from January 2014 to December 2019 and met the inclusion criteria. The patients were divided into survival group ( n=23, 17 males and 6 females, aged 41 (31, 51) years) and death group ( n=14, 11 males and 3 females, aged 50 (43, 58) years) according to the prognosis of within 60 d after burn. Basic data of patients in the two groups and their routine coagulation indexes during shock period including prothrombin time (PT), thrombin time, activated partial thromboplastin time (APTT), D-Dimer, fibrinogen degradation product (FDP), fibrinogen, platelet, and international normalized ratio (INR) were recorded. Data were statistically analyzed with Wilcoxon rank sum test and Fisher′s exact probability test, prognosis-related factors was analyzed with single factor and multivariate logistic regression analysis (α selected=0.05, α excluded=0.1), and receiver operating characteristic (ROC) curve analysis were established to screen out the risk factors. All the patients were grouped into high score group and low score group according to the optimal threshold value, Kaplan-Meier method was used for survival analysis and Log-rank test was performed between the two groups. Results:Total burn surface area (TBSA) of patients in death group was obviously larger than that in survival group ( Z=2.980, P<0.01), while there were no statistically significant difference in the other indexes between the two groups ( P>0.05). Compared with those in survival group (16.10 (14.30, 16.90) s, 40.80 (36.20, 42.80) s, 1.30 (1.10, 1.40)), PT (18.70 (16.30, 22.70) s), APTT (46.45 (41.00, 57.10) s) and INR (1.55 (1.30, 1.96)) of patients in death group were significantly increased ( Z=2.540, 2.330, 2.300, P<0.05), there were no statistically significant difference in the other indexes between the two groups ( P>0.05). Single factor logistic regression analysis showed TBSA, PT, and APTT were factors related to death of adult patients with extensively severe burn within 60 d after burn (odds ratio (OR)=1.190, 1.214, 1.109, 95% confidence interval (CI)=1.053-1.346, 1.008-1.461, 1.012-1.215, P<0.05 or P<0.01). FDP and INR were potential factors related to death of adult patients with extensively severe burn within 60 d after burn (OR=1.040 and 4.559, 95% CI =0.998-1.083 and 0.918-22.641, P<0.1). Multivariate logistic stepwise regression was used to build models of APTT+ FDP+ TBSA and APTT+ FDP. Area under the curve (AUC) of APTT+ FDP+ TBSA model score was 0.944 (95% CI= 0.873-1.000), which was higher than AUC of APTT+ FDP model score (0.843, 95% CI=0.713-0.973) by ROC curve analysis. Optimal threshold value of APTT+ FDP+ TBSA model score was -0.879 4 with sensitivity of 100% (95% CI=100%-100%) and specificity of 87% (95% CI=74%-100%). Survival ratio of patients in high score group with optimal threshold value higher than -0.879 4 was significantly lower than that in low score group with optimal threshold value lower than -0.879 4, χ2=27.090, P<0.01. Conclusions:The coagulation state of adult patients with extensively severe burn in shock stage is characterized with procoagulant and hemostatic dysfunctions accompanied by enhanced fibrinolytic activity. The risk of death is significantly increased in adult patients with extensively severe burn with APTT+ FDP+ TBSA model score higher than -0.879 4.
4.Selection of parameters of narrowband ultraviolet B phototherapy for vitiligo
Ai'e XU ; Jiehao LEI ; Qimin FAN
Chinese Journal of Dermatology 2020;53(2):89-92
Narrowband ultraviolet B has been applied to the treatment of vitiligo for more than 10 years in China.Currently,there are no consistent standards for clinical treatment parameters,and patients cannot benefit from non-standard treatment,which is liable to cause erythema,blisters,photoaging and other adverse reactions.Based on the Vitiligo Working Group recommendations for narrowband ultraviolet B phototherapy for vitiligo,relevant literature and clinical experiences,the authors discuss parameters of narrowband ultraviolet B phototherapy for vitiligo from the aspects of treatment frequency,initial dosing,dose adjustment during consecutive treatment or after missed treatment,response plateau,treatment course and maximum acceptable number of phototherapy,so as to improve the efficacy of narrowband ultraviolet B phototherapy for vitiligo.
5.Association between efficacy of and response to narrow-band ultraviolet B phototherapy as well as factors related to phototherapy response in patients with vitiligo
Jiehao LEI ; Qimin FAN ; Rong CHEN ; Ai'e XU
Chinese Journal of Dermatology 2019;52(4):259-262
Objective To evaluate the association between clinical efficacy of and response to narrow-band ultraviolet B (NB-UVB) phototherapy in patients with confirmed vitiligo,and to identify factors influencing phototherapy response.Methods From January 2017 to March 2018,a total of 104 patients with vitiligo,who received NB-UVB phototherapy at the Department of Dermatology,Hangzhou Third Hospital,Zhejiang University of Traditional Chinese Medicine,were enrolled into this study.Among them,there were 55 males and 49 females,with an average age of 32.06 years (range:4-64 years).Their course of disease ranged from 2 months to 27 years,and the average course of disease was 8.15 years.The phototherapy sessions required to achieve initial repigmentation and to enter the plateau phase during which repigmentation ceased to increase with treatment sessions (plateau photothereapy sessions),as well as effective phototherapy sessions (the difference between the phototherapy sessions required to achieve initial repigmentation and those to enter the plateau phase) were recorded.Rank sum test was used to analyze the difference in the above phototherapy sessions between patients with different response,and multiple linear regression analysis to identify factors influencing plateau photothereapy sessions and effective phototherapy sessions.Results All the 104 patients were followed up.Among them,2 patients achieved complete repigmentation,1 showed no response to the phototherapy,and the remaining 101 patients were enrolled into the analysis.Among the 101 patients,52 achieved ≥ 50% repigmentation (high efficacy group),and 49 achieved < 50% repigmentation (low efficacy group).Compared with the low efficacy group,the high efficacy group showed significantly less phototherapy sessions required to achieve initial repigmentation (M [P25,P75],8 [7,10] vs.10[8,13],Z =3.125,P =0.002),but significantly more plateau phototherapy sessions (41 [29,60] vs.35 [26,44],Z =-3.375,P < 0.001) and effective phototherapy sessions (32 [18,51] vs.24 [8,36],Z =-4.407,P < 0.001).Multiple linear regression analysis showed that the total number of plateau phototherapy sessions was positively correlated with vitiligo area (β =0.360,t =2.698,P =0.008) and duration of disease (β =0.215,t =2.325,P =0.022),but negatively correlated with vitiligo disease activity score (VIDA) (β =-2.665,t =3.969,P < 0.001).Moreover,the number of effective phototherapy sessions was positively correlated with vitiligo area (β =0.358,t =2.582,P =0.011) and duration of disease (β =0.216,t =2.276,P =0.025),but negatively correlated with VIDA (β =-2.669,t =-3.935,P < 0.001) and phototherapy sessions required to achieve initial repigmentation (β =-1.011,t =-4.508,P < 0.001).Conclusions During the treatment with NB-UVB,the less the number of phototherapy sessions required to achieve initial repigmentation is,the more the number of effective phototherapy sessions is,and the better the efficacy of NB-UVB phototherapy is.Vitiligo area,duration of disease and clinical staging may provide the basis for predicting phototherapy sessions required to enter the plateau phase.
6.Efficacy of home versus hospital narrow-band ultraviolet B phototherapy for vitiligo
Jiehao LEI ; Qimin FAN ; Ai'e XU
Chinese Journal of Dermatology 2018;51(10):749-751
Objective To compare the efficacy and acceptance of home versus hospital narrowband ultraviolet B (NB-UVB) phototherapy for vitiligo.Methods Eighty patients with vitiligo were collected at the Department of Dermatology of Hangzhou Third Hospital from August 2016 to September 2017,and randomly and equally divided into two groups to be treated with home (home NB-UVB group) or hospital NB-UVB phototherapy (hospital NB-UVB group) twice a week for 36 sessions.After the treatment,the efficacy,adverse reactions and patient acceptance were evaluated.Results Finally,39 patients in the home NB-UVB group and 37 in the hospital NB-UVB group completed the treatment.The response rates in the face and neck,trunk and extremities were 62.5%,48.6% and 42.3% respectively in the home NB-UVB group,and were 66.7%,55.9% and 48.6% respectively in the hospital NB-UVB group.There were no significant differences in the response rate,cumulative dosage required for initial repigmentation and cumulative dosage at the end of treatment at the same body site between the 2 groups.The incidence of adverse reactions was significantly higher in the home NB-UVB group than in the hospital NB-UVB group (61.5% vs.24.3%,P < 0.05),and the duration of a single treatment was significantly shorter in the home NB-UVB group than in the hospital NB-UVB group (27.95 min vs.129.73 min,P < 0.05).Multiple linear regression analysis showed that the patient acceptance in the home NB-UVB group significantly increased along with the improvement of efficacy (β =0.483,t =4.573,P < 0.001),but decreased along with the increase of treatment duration (β =-0.569,t =-5.831,P < 0.001).However,the patient acceptance in the hospital NB-UVB group significantly increased along with the improvement of efficacy (β =0.758,t =7.547,P < 0.001),but was not correlated with the treatment duration (β =-0.204,t =-2.030,P =0.05).Conclusions The home and hospital NB-UVB phototherapy can complement each other for the treatment of vitiligo.Appropriate therapy should be chosen for different patients,so as to enhance patient compliance,which is an essential condition for the improvement of efficacy.
7.Effects of RhoA gene silencing by RNA interference on invasion of tongue carcinoma.
Zhenggang CHEN ; Yong-ping TANG ; Lei TONG ; Ying WANG ; Yuan ZHOU ; Qimin WANG ; Jinhong HAN ; Zongxuan HE ; Yixiang LIAO ; Bing FAN ; Rong-hai ZOU ; Jian ZHANG ; Xiaofeng SUN ; Guoxin YAN
West China Journal of Stomatology 2016;34(2):183-188
OBJECTIVETo study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4.
METHODSDetermination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma.
RESULTSRhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well.
CONCLUSIONRhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.
Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Down-Regulation ; Galectin 3 ; metabolism ; Gene Silencing ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Tongue Neoplasms ; genetics ; metabolism ; pathology ; Transfection
8.Random Forests algoritm-based bioinformatic screening of functional genes involved in lymph metastasis of cervical cancer
Shuying FAN ; Chunxiao LI ; Ting WANG ; Chunxia ZHOU ; Haili QIAN ; Haijuan WANG ; Qimin ZHAN
Chinese Journal of Biochemical Pharmaceutics 2016;36(4):5-8
Objective To screen the genes most relevant to lymph node metastasis of cervical cancer and identify the genes at the key knots of the regulatory network to provide the potential targets for cervical cancer intervention.Methods The transcriptional profiling database of TCGA was used, and random forests algorithm was adopted to rank the genes related to lymph node metastasis extracted from GeneCards database.STRING and Cytospace tolls were used to build the interactive regulatory network and identify the most weighted genes localized in the central of the network.DAVID platform was used to perform a functional annotation for the whole geneset.Results We ranked 2784 genes in respect to their potential contributions to lymph node metastasis of cervical cancer and identified the genes at the key knob.The genes related to cancer metastasis were enriched to cytokines pathway, MAPK pathway, wnt pathway, intercellular interaction, adhesive conjunction, cellular skeleton regulation, etc.Some of the identified key genes, like EGFR, NOTCH1, RHOA, etc. have been verified to be closely related cervical cancer metastasis in the basic and clinical research. Conclusion Random forests algorithm is useful, taking advantages of TCGA database, in enriching the genes playing significant role in cervical cancer metastasis.A majority of the genes in the analyzed geneset were indicated to be significantly correlated with lymph node metastasis.
9.Efficacy of different courses of NB-UVB phototherapy on the treatment of vitiligo
Acta Universitatis Medicinalis Anhui 2016;51(6):916-918
To evaluate the efficacy of different courses of Narrowband Ultraviolet B phototherapy ( NB-UVB) in the treatment of vitiligo .50 vitiligo patients who had finished 3 courses of phototherapy and met the inclusion criteria were included in our study .Each course contained at least 30 times of phototherapy , and between two courses , there was a rest of 3~6 months .The repigmentation of each vitiligo lesion after every course of phototherapy was recorded .To the same lesion , the efficacy difference between the first course and the second course was not statisti -cally significant.But the efficacy of the first course was better than the third course (P<0.05),while the efficacy of the second course was also better than the third course ( P<0.05 ) .There was no significant difference among the three courses concerning the average single irradiation dose .In conclusion , when using NB-UVB in treating vitili-go, the efficacy of first course was equivalent to the second course , but it reduced in the third course .Whenever a plateform stage occurs , a rest of more than 3 months is long enough for the vitiligo lesion to recover initial light sen-sitivity.
10.Efficacy of 308-nm excimer laser combined with topical tacrolimus cream for the treatment of childhood vitiligo on the face or neck
Huili HU ; Qimin FAN ; Junfan CHEN ; Aie XU
Chinese Journal of Dermatology 2013;(1):54-55
Objective To assess the efficacy and safety of 308-nm excimer laser combined with topical tacrolimus 0.03% cream for the treatment of childhood vitiligo on the face or neck.Methods Sixty-eight children aged < or =14 years with vitiligo on the face or neck were enrolled in this study,and divided into two groups based on lesional sites,i.e.,skin group with lesions on the forehead,cheek,lower mandible,neck or in the periortic region and mucosa group with lesions in the perioral or periorbital region.All the patients received 308-nm excimer laser irradiation once or twice weekly and topical tacrolimus 0.03% cream twice daily.Twenty sessions of irradiation served as a treatment course.Efficacy was evaluated at the end of the treatment course.The effects of erythema reaction and cumulative irradiation dose on efficacy were assessed.Results After 20 times of laser therapy,an excellent response was achieved in 78.4% of the patients in the skin group,and 54.8% in the mucosa group (P < 0.05).During the treatment,the average frequency of erythema reaction lasting 48 hours or longer was significantly lower in the skin group than in the mucosa group (5.84 vs.9.12,P < 0.01).After 10 and 20 times of laser therapy,the cumulative radiation dose was 4215 mJ/cm2 and 10 453 mJ/cm2 in the skin group,respectively,compared to 3364 mJ/cm2 and 7430 mJ/cm2 in the mucosa group,respectively (both P < 0.01).Conclusions The 308-nm excimer laser combined with topical tacrolimus cream is effective and safe for the treatment of childhood vitiligo on the face or neck.Vitiligo on the forehead,cheek,lower mandible,neck and in the periortic region appears to respond better to this therapy with a weaker erythema reaction than that in the perioral or periorbital region.

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