Role of folliculin in interferon-γ-mediated apoptosis of and chemokine secretion by melanocytes / 中华皮肤科杂志

Objective:To investigate the role of folliculin in apoptosis of and chemokine secretion by melanocytes mediated by interferon-γ (IFN-γ) .Methods:Normal primary melanocytes were isolated from circumcised foreskin tissues from a healthy male child, and primary vitiliginous melanocytes were isolated from normally pigmented suction-blistered epidermis from patients with vitiligo after suction blister epidermal grafting. Western blot analysis was performed to determine the folliculin protein expression in normal primary melanocytes, primary vitiliginous melanocytes and a human primary melanocyte line PIG1. PIG1 cells stimulated with 10 ng/ml IFN-γ for 48 hours served as induction group, and untreated PIG1 cells served as control group. Real-time quantitative RCR (qRT-PCR) was performed to determine the mRNA expression of folliculin, autophagy-related microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ and Beclin genes, and Western blot analysis to determine the protein expression of folliculin, Beclin1 and LC3Ⅱ/Ⅰ, as well as phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in the above cells. Furthermore, the melanocytes stimulated with 10 ng/ml IFN-γ for 48 hours were divided into several groups: negative control group infected with an empty lentiviral vector, folliculin inhibition group infected with a folliculin-inhibiting lentivirus, autophagy enhancement group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with a mTOR inhibitor, autophagy inhibition group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with an AMPK inhibitor. Then, flow cytometry was conducted to detect apoptosis of PIG1 cells, and enzyme-linked immunosorbent assay to measure the concentration of chemokines CXCL10 and CCL20 in the culture supernatant of PIG1 cells in the above groups. Measurement data were compared among multiple groups by using one-way analysis of variance, and multiple comparisons were carried out by using least significant difference- t test. Results:The relative protein expression level of folliculin significantly differed among the normal primary melanocytes (0.850 ± 0.120) , primary vitiliginous melanocytes (1.507 ± 0.170) and PIG1 cells (0.697 ± 0.130; F = 50.09, P < 0.001) , and was significantly higher in the primary vitiliginous melanocytes than in the normal primary melanocytes and PIG1 cells ( t = 4.06, 5.89, respectively, both P < 0.01) . Compared with the control group, the induction group showed significantly increased relative mRNA and protein expression levels of folliculin (both P < 0.01) , but significantly decreased relative mRNA and protein expression levels of LC3Ⅱ and Beclin (all P < 0.01) ; moreover, the induction group showed significantly decreased LC3Ⅱ/Ⅰ levels (0.72 ± 0.02) and AMPK phosphorylation levels (0.714 ± 0.023) in the PIG1 cells compared with the control group (1.13 ± 0.02, 1.176 ± 0.002, t = 7.34, 6.67, respectively, both P < 0.01) , but significantly increased mTOR phosphorylation levels (1.051 ± 0.023) compared with the control Group (0.451 ± 0.016, t = 3.81, P = 0.009) . There were significant differences in the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 among the control group, induction group and other treatment groups (all P < 0.001) ; specifically, the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 were significantly higher in the induction group than in the control group, lower in the folliculin inhibition group than in the negative control group, lower in the autophagy enhancement group than in the folliculin inhibition group, and higher in the autophagy inhibition group than in the folliculin inhibition group (all P < 0.05) . Conclusions:Folliculin is highly expressed in vitiliginous melanocytes. Folliculin expression and downstream signaling pathways are regulated by IFN-γ, and folliculin may participate in IFN-γ-mediated melanocyte apoptosis and chemokine secretion via regulating autophagy.

Robot-assisted training can improve the bladder and intestinal functions of paraplegic patients / 中华物理医学与康复杂志

Objective To explore the clinical effect of training assisted by a lower limb rehabilitation robot on the bladder and intestinal function of paraplegic spinal cord injury survivors. Methods Thirty-eight paraplegic patients with spinal cord injury were divided according to their admission order into an experimental group ( n=19) and a control group (n=19). Both groups were given conventional rehabilitation training, while the experimental group was additionally provided with robot-assisted lower limb training in three stages:adaptation, training and con-solidation. It lasted 30 minutes daily, 5 days per week for 12 weeks. Before and after the training, an urodynamics examination system was used to evaluate the maximum urine flow, bladder capacity, residual urine volume, bladder pressure and detrusor pressure. Colon transit time, mean rectal pressure and intestinal function were measured using the colon transit test, a mean rectal pressure test, and the Functional Independence Measure ( FIM) scale respective-ly. Results The average bladder volume, maximum urine flow rate, average urine flow rate, detrusor pressure, bladder compliance, average rectal pressure and intestinal FIM score of the robot training group after training were all significantly better than before the training, as were the average residual urine volume and colon transit time. After the training, the average bladder volume, maximum urine flow rate, average urine flow rate, detrusor pressure, bladder compliance and average rectal pressure of the robot training group were all significantly higher than those of the control group, while the average residual urine volume and colon transit time were significantly smaller. Then, 32％ of the patients in the experimental group achieved no less than 6 points for their average FIM score, significantly higher than in the control group. Conclusion Robot-assisted lower limb training combined with comprehensive rehabilitation training can effectively improve the bladder and intestinal function of paraplegic patients after a spinal cord injury.

miR-593 inhibits proliferation of colon cancer cells by down-regulating PLK1 / 南方医科大学学报

OBJECTIVE@#To explore the role of miR-593 in regulating the proliferation of colon cancer cells and the molecular mechanism.@*METHODS@#Bioinformatics analysis identified PLK1 as the possible target gene of miR-593. Luciferase assay was employed to verify the binding between miR-593 and PLK1, and qRT-PCR and Western blotting were used to verify that PLK1 was the direct target gene of miR-593. CCK-8 assay was performed to test the hypothesis that miR-593 inhibited the proliferation of colon cancer cells by targeting PLK1.@*RESULTS@#Luciferase assay identified the specific site of miR-593 binding with PLK1. Western blotting showed a significantly decreased expression of PLK1 in the colon cancer cells transfected with miR-593 mimics and an increased PLK1 expression in the cells transfected with the miR-593 inhibitor as compared with the control cells ( < 0.05). The results of qRT-PCR showed no significant differences in the expression levels of PLK1 among the cells with different treatments ( > 0.05). The cell proliferation assay showed opposite effects of miR-593 and PLK1 on the proliferation of colon cancer cells, and the effect of co-transfection with miR-593 mimic and a PLK1-overexpressing plasmid on the cell proliferation was between those in PLK1 over-expressing group and miR-593 mimic group.@*CONCLUSIONS@#miR-593 inhibits the proliferation of colon cancer cells by down-regulating PLK1 and plays the role as a tumor suppressor in colon cancer.

Short-term efficacy and predictive factors of BCG instillation in high risk non-muscle invasive bladder cancer / 中华泌尿外科杂志

Objective To investigate the short-term efficacy,safety and factors affecting the efficacy of BCG intravesical therapy in high risk non-muscle-invasive bladder cancer (NMIBC) patients.Methods A total of 161 high-risk non-muscle invasive bladder cancer (NMIBC) patients were reviewed in our hospital from March 2014 to December 2017.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).There were 121 males (75.2％) and 40 females (24.8％).Median age was 65 years old,including 17 cases (10.6％) ＜50 years old,23 cases (14.3％) within 50-59 years old,72 cases (44.7％) within 60-69 years old,49 cases ≥70 years old (30.4％).There were 112 patients (69.6％) with primary bladder cancer and 49 (30.4％) patients with recurrent bladder cancer.56 cases (34.8％) had single tumor and 105 cases (65.2％) had multiple tumors.The tumors size in 106 cases (65.8％) was less than 3 cm,and tumor size in 55 cases (34.2％) was more than 3 cm.43 patients (26.7％) suffered carcinoma in situ.10 patients (6.2％) suffered urothelial carcinoma with variant types.According to the American Joint Commission for Cancer (AJCC) version 7 TNM staging system,25 cases (15.5％) were classified into Ta stage,129 cases (80.1％) were classified into T1 stage,and 7 cases (4.3％) were classified into Tis stage.There were 8 cases (5％) with low-grade cancer and 153 cases (95％) with high-grade cancer.69 patients (42.9％) received chemo-instillation before.43 cases were directly perfused without re-TURBT and 118 cases were perfused after re-TURBT.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).The 120 mg BCG were dissolved into 50 ml saline for instillation and were kept for 2 hours.Induction scheme of six-weekly and three fortnightly instillations started two weeks after the initial TUR or re-TUR.Maintenance instillations were then be offered in a scheme of ten monthly instillations.During treatment,patients were offered cystoscopy and cytology every three months,while CT and chest radiographs were reviewed every 6-12 months.Recurrence status and adverse effects were recorded.Univariate and multivariate regression analyses were performed to predict risk factors for failure of BCG instillation in bladder cancer.Results A total of 161 patients were followed up.The median follow-up time was 13 months,ranging 7-22 months.The overall recurrence rate was 26.1％ (42/161) and the 1-year recurrence-free survival rate was 79.0％.On univariate analysis,recurrence history,history of instillation chemotherapy application and history of re-staging transurethral resection influenced recurrence.Multivariate regression analysis showed recurrence status was an independent prognostic factor regarding recurrence-free survival.The incidence of adverse events in all 161 instillation patients was 40.4％ (26/65).Grade 1,grade 2 and grade 3 adverse events accounted for 53.8％ (35/65),40.0％ (26/65) and 6.2％ (4/65) respectively.6 cases (3.7％) reduced the dose of BGC and 1 case stop the instillation due to the intolerance of BCG.Conclusion Short-term efficiency and safety were confirmed in BCG-treated high-risk NMIBC patients.And recurrence status was an independent prognostic factor for recurrence-free survival.

Protective effect of WSY6, a caffeic acid derivative, on oxidative stress injury in melanocytes and its mechanism / 中华皮肤科杂志

Objective To evaluate the protective effect of WSY6 (a caffeic acid derivative) on hydrogen peroxide (H2O2)-induced oxidative stress injury in melanocytes,and to explore its potential molecular mechanism.Methods In vitro cultured human primary melanocytes were divided into 5 groups:control group receiving no treatment,H2O2 group treated with 1 mmol/L H2O2,6.25,12.5,25 μmol/L WSY6 groups pretreated with 6.25,12.5,25 μmol/L WSY6 respectively followed by 1-hour treatment with 1 mmol/L H2O2.After 24-hour treatment,MTS assay was performed to determine the survival rate of melanocytes,and the lactate dehydrogenase (LDH)kit was used to detect the LDH leakage level.Some melanocytes were divided into 2 groups:inhibitor group pretreated with the p38 inhibitor for 1 hour followed by 1-hour treatment with 1 mmol/L H2O2,and H2O2 group treated with 1 mmol/L H2O2 for 1 hour.After 24-hour treatment,the LDH kit was used to detect the LDH leakage level.Some other melanocytes were pretreated with 25 μmol/L WSY6 for 1,2,4 hours separately,followed by 1-hour treatment with H2O2.Then,flow cytometry was conducted to detect the level of intracellular reactive oxygen species (ROS).Some melanocytes were treated with 6.25,12.5,25 μmol/L WSY6 separately for 1 hour,followed by 1-hour treatment with H2O2.Then,Western bolt analysis was performed to determine the protein expression of cytochrome c (cyto-c),caspase-3,caspase-9,phosphorylated (p)-p38 MAPK,p-ERK and p-JNK.Results Compared with the control group,the H2O2 group showed significantly decreased survival rate of melanocytes (29.22％ ± 1.31％,P ＜ 0.05),but significantly increased intracellular LDH leakage level (47.19％ ± 4.85％,P ＜ 0.05),elevated intracellular ROS level (18.37 ± 1.59,P ＜ 0.05),and increased expression of caspase-3 and caspase-9.Compared with the H2O2 group,the 6.25,12.5,25 μmol/L WSY6 groups showed significantly increased cell survival rate (52.48％ ± 1.17％,60.21％ ± 0.25％,78.32％ ± 1.73％,P ＜ 0.05),but significantly decreased LDH leakage level (21.99％ ± 0.22％,15.38％ ± 0.45％,13.18％ ± 0.38％,P ＜ 0.05),and the intracellular ROS level was significantly decreased in the 25 μmol/L WSY6 group after 1,2,4 hours of treatment (7.59 ± 1.00,6.22 ± 0.52,5.1 ± 0.48,P ＜ 0.05).The LDH leakage level in melanocytes was significantly lower in the p38 inhibitor group than in the H2O2 group (P ＜ 0.05).Western blot analysis revealed that after the pretreatment with 6.25,12.5,25 μmol/L WSY6 separately,the WSY6 groups all showed obviously decreased expression of caspase-3,caspase-9 and p-p38 compared with the H2O2 group.However,there was no obvious difference in the expression of p-ERK and p-JNK between the WSY6 groups and the H2O2 group.Besides,the WSY6 groups showed decreased expression of p-p53 (a downstream product of p38 MAPK),which decreased along with the increase in the concentration of WSY6.Conclusion WSY6 shows a markedly protective effect on H2O2-induced oxidative stress injury in melanocytes,likely through the p38 MAPK pathway.

The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer / 中国癌症杂志

Background and purpose:Liquid biopsy is a kind of blood, urine and other non-solid biologi-cal tissue sampling analysis, mainly for malignant tumor diagnosis, monitoring and predicting its prognosis. In this research, we optimized the extraction of miRNA in urine, established a standardized means of liquid biopsy, screened and verified the miRNA markers in patients with bladder cancer.Methods:From Jan. 2014 to Sept. 2015, we used miRNA microarray in six patients with bladder cancer and six healthy controls. Samples of 78 cases of bladder cancer and 23 healthy controls were tested by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) to verify the relationship between miRNA markers in liquid biopsy and clinical pathological parameters. The diagnostic value of miRNA markers was also analyzed and compared.Results:We screened 10 miRNAs differential expression in urine. Combined with previous literature, we selected 20 miRNAs to verify their expression levels in bladder cancers and healthy controls. miR-509-5p/miR-124 ratio in the urine was found higher in patients with bladder cancer than in healthy controls (P<0.0001). With the rise of miR-509-5p/miR-124 ratio in urine, tumor stage and grade were also increased (P=0.003). When the cutoff was set at 0.41, the diagnostic sensitivity and specificity of miR-509-5p/miR-124 ratio were 73.1% and 82.6%, respectively. The AUC of miR-509-5p/miR-124 ratio to detect bladder cancer was 0.864, higher than that of urinary exfoliated cells (P=0.0002).Conclusion:We optimized the extraction of miRNAs in urine,established a standardized liquid biopsy of miRNA markers. The miR-509-5p/miR-124 ratio could be an ideal diagnos-tic marker for bladder cancer.

Long noncoding RNAs in urological neoplasms / 中国癌症杂志

Long non-coding RNAs (lncRNAs) are deifned as transcripts longer than 200 nt without coding capacities. Although they were initially argued to be transcriptional by-products of RNA polymeraseⅡ, recent evidence suggests that lncRNAs have been associated with a spectrum of biological processes, and aberrant lncRNA expression may be a major contributor to tumorigenesis, progression and prognosis. This study summarizes the up-to-date studies on lncRNAs in urological neoplasms.

The application value of hysteroscopy in recurrent implantation failure / 中国基层医药

Objective To explore the application value of hysteroscopy in recurrent implantation failure ,and discuss what was the best time to transfer embryos after the operation .Methods The patients who had undergone two or more failed IVF-ET cycles were separated into two groups .The patients of group A ( n=210) received hysteroscopy , and the patients of group B ( n=71) did not receive hysteroscopy evaluation .Intrauterine lesions diagnosis were trea-ted during the procedure .Patients without intrauterine pathologies were given slight curettage .The recurrent IVF-ET were performed after the procedure .Then we analyzed the clinical pregnancy rate of the two groups and determined the best time to transfer embryos after the operation.Results In group A,57 patients were pregnant.In group B, 8 patients were pregnant .There was a significant difference in the clinical pregnancy rates between the two groups (χ2 =7.52,P<0.01).In the pregnant patients of group A ,about 94.7%were pregnant in 6 months after hysterosco-py.Conclusion The patients with recurrent IVF -ET transfer failure should be evaluated prior to commencing IVF-ET cycle to improve the clinical pregnancy rate .It is better to transfer embryos within 6 months after hysteroscopy operation.

Laparoscopic retroperitoneal adrenalectomy for adrenal mass：report of 130 cases / 中国癌症杂志

Background and purpose:Laparoscopic retroperitoneal adrenalectomy makes access to the adrenal glands easier and less invasive than open surgery. The aim of this study was to evaluate the clinical efifcacy of laparoscopic retroperitoneal adrenalectomy.Methods:A total of 130 patients who underwent retroperitoneal adrenalectomy for adrenal mass from Jan. 2007 to Dec. 2012 in Fudan University Shanghai Cancer Center were retrospectively assessed. Their clinicopathological factors, perioperative complications and short-term prognostic data were retrieved from the medical records.Results:One hundred and twenty-seven of 130 patients underwent retroperitoneal adrenalectomy successfully, and 3 patients were converted to open surgery due to severe bleeding. Among 130 patients, 63 were male and 67 were female, with the mean age 50.0 years. The pathological results of the 130 patients indicated adrenocortical adenoma in 68, pheochromocytoma in 15, medullary lipoma in 13, adrenal cysts in 10 , ganglioneuroma in 7, metastatic cancer in 5, adrenal hyperplasia in 4, schwannoma in 3, lymphangioma in 2, adrenal hematoma in 1, adrenal cortical carcinoma in 1, adrenal angiosarcoma in 1 and the deputy spleen in 1 (one patient suffering from both pheochromocytoma and ganglioneuroma). The maximum diameters were ranging from 0.5 to 9.0 cm, and mean diameter was 3.48 cm. The average blood loss in surgery was 62.73 mL. Mean length of stay in hospital was 7 d. GradeⅠ complications occurred in 5 patients, including 2 of fever, 1 of food allergy, 1 of drug allergy and 1 of hypokalemia.Conclusion: Retroperitoneal adrenalectomy should be considered as the procedure of choice for the resection of most adrenal tumors in skilled centers with the advantages of minimal invasion, increased safety and faster recovery.

Relationship between UGT1A1 * 28 gene polymorphism and delayed diarrhea caused by FOLFIRI treatment / 国际肿瘤学杂志

Objective To analyze the relationship between UDP-glucuronosyltransferase 1A1 (UGT1A1)gene polymorphism and delayed diarrhea caused by FOLFIRI treatment.Methods Two hundred and one blood samples were taken from patients with metastatic digestive tract tumor before chemotherapy by FOLFIRI and then the UGT1A1 * 28 genetic polymorphism was performed.All the cases treated with FOLFIRI were chosen to be observed and recorded by situation of the delayed diarrhea during chemotherapy,and to analyze the relationship between UGT1A1 * 28 genetic polymorphism and grade 3 and 4 delayed diarrhea.Results The distributions of the genotypes in 201 metastatic digestive tract tumor patients were as follows:UGT1A1 * 28 wild-type genotype TA6/6 (155,77.11％),heterozygous genotype TA6/7 together with homozygous genotype TA7/7 (46,22.89％).In the 201 cases,the incidences of grade 1 and 2 delayed diarrhea in the patients carrying wild-type genotype and mutant type were respectively 45.16％ (70/155),39.13％ (18/46).The incidences of grade 3 and 4 delayed diarrhea were respectively 9.68％ (15/155),19.57％ (9/46),with no statistical difference (x2 =3.318,P =0.190).Conclusion The UGT1A1 * 28 polymorphism TA6/7 or TA7/7 can not increase the risk of grade 3 or more severe delayed diarrhea for the patients with metastatic digestive tract tumor after receiving FOLFIRI treatment.

Comparison of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for the treatment of monobenzone-induced vitiligo-like depigmentation in a mouse model / 中华皮肤科杂志

Objective To compare the therapeutic effect of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for monobenzone-induced vitiligo-like depigmentation in mice.Methods Twentyfive 3-week-old female C57BL/6 mice were randomly and equally divided into 5 groups:negative control group,model group,tea polyphenol group,pimecrolimus group,tacrolimus group.Monobenzone 45％ cream was applied to the back of mice in all the five groups except the negative control group once daily for 40 consecutive days to establish a model of vitiligo-like depigmentation.During the induction of depigmentation,the tea polyphenol group,pimecrolimus group and tacrolimus group were topically treated with tea polyphenol,pimecrolimus and tacrolimus respectively,and the model group remaining untreated.The depigmentation of hairs and skin was observed by naked eyes on a daily basis.Tissue specimens were obtained for histological examination from depigmented skin at nonapplication sites in mice after the end of the experiment.Hematoxylin-eosin staining was conducted to analyze lymphocytic infiltration,reflectance confocal microscopy to observe melanin and melanocytes in skin,and immunofluorescence assay to detect CD8+ T cell infiltration.Results Depigmentation occurred in both application sites and non-application sites of mice in the model group.Compared with the model group,the tacrolimus,pimecrolimus and tea polyphenol groups showed delayed depigmentation,reduced degree and area index of depigmentation,and attenuated lymphocytic infiltration and CD8 + T cell infiltration in depigmented maculae at application sites.In addition,the therapeutic effect of tacrolimus was stronger than that of pimecrolimus and tea polyphenol.Conclusion Tea polyphenol,pimecrolimus and tacrolimus are all effective for the treatment of vitiligolike depigmentation in mice.

Effect of halometasone in combination with scutellaria baicalensis georgi on the vitiligo mice / 中国药理学通报

Aim To study the effect of halometasone in combination with scutellaria baicalensis georgi on the vitiligo mice induced by monobenzone. Methods 40% monobenzone cream was applied to induce vitiligo in C57BL/6 mice. Through the halometasone, halo-metasone and scutellaria baicalensis georgi combined with 40% monobenzone cream, the influence of halo-metasone and scutellaria baicalensis georgi on mice de-colorizing was studied. Hair decolorizing was observed with the naked eye, the skin decolorizing was observed by reflectance confocal microscopy ( RCM ) , and CD8 +T cell infiltration was tested with immunofluores-cence detection. The serum levels of interleukin-6(IL-6 ) and tumor necrosis factor-α( TNF-α) were deter-mined by enzyme linked immunosorbent assay ( ELISA) . Results Mice in model group showed de-pigmentation at both the monobenzone application part and non-application part. The halometasone group did not show significant therapeutic efficacy. In halometa-sone and scutellaria baicalensis georgi treatment group, there was less decolorization, the occurrence ratio, the scores of occurring time and size were lower compared with model group. There were fewer infiltrated lympho-cytes and CD8 +T cells. Halometasone and scutellaria baicalensis georgi group also showed that the serum levels of IL-6,TNF-α decreased. Conclusion Halo-metasone and scutellaria baicalensis georgi have thera-peutic effect on vitiligo mice induced by monobenzone.

Effect of local acupuncture on monobenzone-induced vitiligo-like depigmentation in mice / 中华皮肤科杂志

Objective To evaluate the effect of injuries on monobenzone-induced vitiligo-like depigmentation in mice.Methods Forty C57BL/6 mice were randomly and equally divided into four groups:negative control group topically treated with vaseline cream,model group induced by topical monobenzone (40％) cream,acupuncture group receiving acupuncture treatment (15 times) once every three days,and acupuncture combined with monobenzone group receiving both monobenzone induction and acupuncture treatment.The treatment lasted 50 days and mice were sacrificed 15 days after the end of treatment.Hair decolorization was observed with naked eyes,and skin decolorization with reflectance confocal microscopy (RCM) on a daily basis.Tissue specimens were obtained from depigmented skin at monobenzone-uninduced sites,and subjected to hematoxylin and eosin (HE) staining for the cvaluation of lymphocytic infiltration as well as immunofluorescence staining for the detection of CD8+ T cell expression.Statistical analysis was done by t test.Results Varying degrees of depigmentation were observed in both monobenzone-induced and-uninduced sites in both the model group and acupuncture combined with monobenzone group,and the latter group showed earlier,larger and more stable depigmentation than the former group.At 15 days after the end of treatment,the decolorization area index in the model group and acupuncture combined with monobenzone group was 3.45 ± 0.17 and 3.90 ± 0.25 at monobenzone-induced sites respectively(t =7.433,P ＜ 0.05),1.90-± 0.12 and 2.85 ± 0.27 at monobenzone-uninduced sites respectively (t =7.529,P ＜ 0.05).Significant differences were observed in the fluorescence intensity of CD8 + T cells at monobenzone-uninduced depigmented sites between the model group and acupuncture combined with monobenzone group (175.528 ± 10.711 vs.645.928 ± 12.652,t =8.105,P ＜ 0.05),and there was a more evident infiltrate with lymphocytes and CD8+T cells in the monobenzone-uninduced depigmented sites in the acupuncture combined with monobenzone group.Conclusion Local destruction of skin barrier may promote monobenzone-induced vitiligo-like decolorization in mice.

Clinical application of complete retrograde radical cystectomy and consequent abdominal cavity reconstruction in male bladder cancer:a report of 110 cases / 中国癌症杂志

Background and purpose:Bladder cancer radical surgery is dififcult with many perioperative complications, and the learning curve is long. To introduce the clinical application of complete retrograde radical cystectomy and consequent abdominal cavity reconstruction in male bladder cancer, and to provide a standardized surgical procedure with minimum perioperative complications and short learning curve. Methods:From Apr. 2012 to Apr. 2013, 110 cases of male patients with bladder cancer received this procedure in our department, with a median age of 64 (35-83) years;Preoperative characters, surgical parameters, perioperative complications, pathology, long-term complications and short-term prognosis were collected and analyzed. Results:The median number of lymph nodes resected in operation was 12 (8-16);Neurovascular bundles were reserved bilaterally in 65 cases, and unilaterally in 31 cases;The complete procedure including urinary diversion took 4.4 (2.2-6.0) hours, with a median time of opened abdominal cavity of 43.0 (5.0-75.0) minutes;The median blood loss was 140.0 (50.0-600.0) mL, and 4 patients needed transfusion; Median time of abdominal and pelvic drainage was 10.0 (6.0-15.0) days, the median gastrointestinal recovery time was 2.5 (1.0-12.0) days, and the median postoperative hospital stay was 17.0 (10.0-39.0) days;Grade 2 Clavien-Dindo classiifcation (CDC) of surgical complications that required medical intervention were found in 19 cases, CDC grade 3 or above were found in 8 cases;Mild to moderate postoperative ileus happened in 5 cases, all recovered in median 2 (1-4) weeks with supportive treatments;There were no perioperative deaths. All samples were sent to pathological analyses. After a median follow-up of 9 (3-15) months, no complications of or above CDC grade 3 happened, and there were no recurrence. Conclusion:Complete retrograde radical cystectomy in male bladder cancer provided clear anatomical approach, reliable neurovascular bundle preservation, less blood loss, limited abdominal organs disturbance and better surgical exposure; With respect to tumor control, more peritoneal was retained for subsequent abdominal cavity reconstruction. The introduced procedure effectively speeded up gastrointestinal recovery, reduced postoperative complications, especially the incidence of ileus and its severity, and shortened hospital stay. The learning curve of this procedure for urologists was short, and further investigation was warranted.

Application of whole body 18F-FDG PET/CT plus additional delayed pelvic scan after oral hydration ;in the diagnosis of the bladder malignant lesions / 中国癌症杂志

Background and purpose: 18F-FDG has been considered to be of limited value for the detection of bladder lesions because of interference by the 18F-FDG excreted in urine. Delayed pelvic images with“diluted and iflled bladder”use a method of 18F-FDG PET/CT with delayed images after oral hydration so as to increase the detection rate of 18F-lfuorodeoxyglucose(FDG) PET/CT imaging for the lesions of bladder. Methods:48 patients with bladder lesions(35 patients with bladder primary tumor and 13 patients with metastatic tumor) underwent 18F-FDG PET/CT detection and were required oral hydration of 1200-1800 mL water, urination frequently, holding urine when the more scan began. Lesions conifrmed by histopathology, MRI, CT or clinical follow-up at least 1 year. Results:89%(43/48) of patients were obtained good clearance and the urine SUVmax declined from 33.14(9-66.80)to 3.23(1.35-5.65) signiifcantly and the statistical difference was signiifcant (t=8.703, P<0.01). The interval time between two scan was 2 h approximately. At the same time, the SUVmax of bladder lesion was 2.8-25.0. Detection sensitivity, speciifcity and accuracy were 90.47%(19/21), 81.48%(22/27)and 85.41%(41/48), respectively. Conclusion: 18F-FDG activity in the bladder signiifcantly decreased in most patients with“diluted and iflled bladder”. The PET/CT scan can highly detect lesions of bladder tissues. Our method with high accuracy and better endurance could be applied to detect the lesions in bladder.

Effect of epigallocatechin gallate and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice / 中华皮肤科杂志

Objective To study the effect of epigallocatechin gallate (EGCG) and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice.Methods Forty C57BL/6 mice were included in this study.Hairs in an area measuring 2 cm × 2 cm in size were shaved on the back of each of these mice.Then,the mice were randomly and equally divided into four groups to be topically treated with vaseline cream (negative control group),monobenzone 40％ cream (model group),EGCG 5％ cream followed by monobenzone 40％ cream (EGCG group),fructus psoraleae 7％ cream followed by monobenzone 40％ cream (fructus psoraleae group),on the shaved area,respectively,for 50 consecutive days.Depigmentation of skin and hairs was observed daily by naked eyes for 15 days after drug withdrawal.At the end of the study,all the mice were sacrificed,and skin specimens were resected from the tested regions in them.Hematoxylin and eosin (HE) staining was performed to observe lymphocyte infiltration,and immunofluorescence assay to estimate the frequency of CD8 + T cells.Results Depigmentation was observed in monobenzone-induced and-uninduced sites in the model group,and in monobenzone-induced sites in all the mice in the EGCG group and fructus psoraleae group,but in neither monobenzone-induced nor-uninduced sites ih the negative control group.The average time for the appearance of depigmentation at monobenzone-induced sites was 16.7,29.3 and 19.9 days in the model group,EGCG group and fructus psoraleae group respectively.The depigmentation area index at monobenzone-induced sites was 4.00 ± 0.00 in the model group,significantly different from that in the EGCG group and fructus psoraleae group (2.11 ± 0.54 and 2.84 ± 0.79,both P ＜ 0.05).Significant differences were also observed in depigmentation area index at monobenzone-induced sites among the model group,EGCG group and fructus psoraleae group (F =14.173,P ＜ 0.05),and at monobenzone-uninduced sites between fructus psoraleae group and EGCG group (P ＜ 0.05).The frequency (expressed as fluorescence intensity) of CD8+ T cells was significantly lower in the EGCG group and fructus psoraleae group than in the model group,and significantly different between EGCG group and fructus psoraleae group (P ＜ 0.05).Conclusions Both EGCG and fructus psoraleae,especially EGCG,can interfere with the induction of vitiligo-like depigmentation of skin and hairs by monobenzone in mice.The mouse model of vitiligolike depigmentaion in this study shows higher similarity to human vitiligo.

Retinoid X receptor signaling pathway in leukemia / 器官移植

Retinoid X receptor (RXR) acts as ligand-dependent transcription factors playing an important role in regulating a serial of physiological processes,such as embryo development and organ homeostasis.At the molecular level,RXRs exert their functions by inter-activating with multiple signal pathways to regulate target gene expression which control cell growth,differentiation,survival and death.The interference in the network of RXR and other signal pathways has turned RXR into an attractive drug target.

Primary graft failure following unrelated cord blood transplantation with high-dose of CD34 + cells in the treatment of AML/MDS / 器官移植

Objective To analysis the cause of primary graft failure of unrelated cord blood transplantation with high-dose of CD34 + cells in treatment of acute myelocytic leukemia (AML) /myelodysplastic syndrome (MDS).Methods A 4-year-old girl was diagnosed AML/MDS at the Department of Pediatric Hematology and Oncology of West China Second University Hospital of Sichuan University. She presented completely remission after induction and consolidation chemotherapy.She received unrelated partially human leukocyte antigen (HLA)-mismatched cord blood transplantation.We investigated the treatment outcomes of UCBT and associated complications.Results The patient suffered primary graft failure and then received secondary haploidentical hematopoietic stem cell transplantation (HSCT)from her mother.However,she suffered fatal multiresistant Acinetobacter spp septicemia.She died due to respiratory failure on 7 d after the second transplantation.Conclusions In this case,hematopoietic stem cells with high dose of CD34 + cells could not overcome the risk of primary graft failure and HLA disparity.The patient's primary graft failure was associated with platelet transfusion refractoriness and potent immunologic dysfunction,especially the anti-HLA donor specific antibodies before unrelated cord blood transplantation.

Analysis of clinical phenotype and genetic mutations of a pedigree of familial hemophagocytic lymphohistiocytosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze mutations in a pedigree of familial hemophagocytic lymphohistiocytosis (FHLH) from Sichuan and provide genetic counseling for the family.</p><p><b>METHODS</b>Clinical data of a case with FHLH diagnosed at West China Second Hospital was retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Eight candidate genes for primary HLH were amplified with PCR and analyzed by direct sequencing.</p><p><b>RESULTS</b>The proband was diagnosed as HLH based on clinical manifestations of recurrent fever for 2 months, hepatosplenomegaly, lymphadenopathy, pancytopenia, hyperferritinemia, and decreased fibrinogen and hemophagocytosis in bone marrow. Genetic testing for primary HLH was carried out considering the relapse of illness after hormone therapy for 8 weeks and the family history. The results of gene sequencing showed that the proband has carried compound heterozygous mutations in PRF1 gene (c.1349C> T in exon 3 and c.445G> A in exon 2). His father has carried a heterozygous mutation (c.445G> A in exon 2) and nonsense mutation (c.900C> T in exon 3), and his mother carried a heterozygous mutation (c.1349C> T in exon 3). Both c.1349C> T and c.445G> A have been previously reported as pathogenic mutations.</p><p><b>CONCLUSION</b>The family has been diagnosed as familial HLH type 2 based on clinical and laboratory examinations and molecular genetic testing. Gene sequencing has indicated that is was a recessive type familial HLH.</p>

Clinical analysis of segmental vitiligo in children / 中华皮肤科杂志

Objective To analyze the clinical features and evolution ot segmental vitiligo in children.Methods A standardized questionnaire was used to clinically investigate segmental vitiligo in 170 children aged ＜ or =12 years and 174 adults with an age of onset ＞ 18 years.Data analysis was done by the software SPSS16.0.Results The female to male ratio was 108:62 in the 170 child patients,significantly different from that in the adult patients (x2 =14.44,P ＜ 0.05).Localized vitiligo occurred as the initial presentation in 82.9％ (141/170) ofthe children and 76.4％ (133/174) of the adults,and progressed into segmental vitiligo in half a year in 76.5％ of the 141 children and 63.9％ of the 133 adults.Vitiligo entered the quiescent stage after half-a-year progression in 71.6％ of the children and 67.3％ of the adults with localized vitiligo as the initial presentation,and after one-month progression in 62.1％ of the children and 41.5％ of the adults with segmental vitiligo as the first presentation (x2 =8.39,P ＜ 0.01).Head and face were affected at the onset of segmental vitiligo in 44.1％ of the childhood cases and 56.9％ of the adult cases.Single nerve segments were involved at the onset in 94.7％ of the child patients and 86.8％ of the adult patients (x2 =0.04,P ＞ 0.05).The proportions of patients with white hairs,autoimmune diseases,and family history were significantly lower in the child patients than in the adult patients (x2 =15.88,5.62,6.66 respectively,all P ＜ 0.05).Conclusions Childhood-onset segmental vitiligo shows a predilection for males,usually presents as localized vitiligo at the onset,and becomes quiescent after half-a-year progression in more than 70％ of patients.