Clinical and genetic analysis of a pedigree with Wolfram syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and genetic background of autosomal recessive Wolfram syndrome caused by WFS1 gene mutation.METHODS: A pedigree with autosomal recessive Wolfram syndrome was studied by clinical examination, gene analysis and bioinformatics.RESULT: It was found that the proband and his brother had diabetes, color weakness and optic neuropathy. In addition, his brother had diabetes insipidus. Whole-exome sequencing(WES)analysis showed that there were two heterozygous variations in the WFS1 gene exon 8 of the two brothers: c.941G>A(p.W314X)and c.2309T>G(p.F770C), and were co-separated from the clinical phenotype in this family.CONCLUSION: The compound heterozygous mutation of WFS1 gene is associated with Wolfram syndrome in this pedigree. Among them, c.941G>A(p.W314X)has not been reported yet.

Pathogenesis of hepatitis B virus-related hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the major malignant tumors that lead to death, and chronic hepatitis B virus (HBV) infection is an important risk factor for HCC. This article introduces the detailed mechanisms of HBV-related HCC, including HBV X protein, immune imbalance, and integration of HBV DNA into the host genome, with a focus on the pathological role and related mechanisms of HBV X protein in HCC. HBV X protein enhances carcinogenesis by promoting tumor cell proliferation, invasion, and metastasis, affecting angiogenesis, promoting cell apoptosis, and interfering with cell metabolism. In-depth studies on the biological functions of HBV X protein, immune imbalance, and HBV DNA integration will help to clarify the pathogenesis of liver cancer and promote the development of novel therapeutic targets for HBV-related HCC.

Silencing LncRNA OIP5-AS1 increases radiosensitivity of non-small cell lung cancer A549 cell line by up-regulating miR-34c-5p expression / 中华放射肿瘤学杂志

Objective To investigate the effect of LncRNA OIP5-AS1 on radiosensitivity of non-small cell lung cancer (NSCLC) cells and its mechanism.Methods The radiation-resistant cell A549R was established by using A549 cells irradiated by X-ray 6Gy in 5 fractions.The expression levels of OIP5-AS1 and miR-34c-5p in A549 and A549R cells were detected by qRT-PCR.OIP5-AS1 inhibitor or miR-34c-5p mimetic was transfected into A549R cells,or OIP5-AS1 overexpression plasmid was transfected into A549 cells.Cell apoptosis was detected by flow cytometry.Cell radiosensitivity was analyzed by colony formation assay.The expression levels of p-Chk2 and p-ATM proteins were measured by Western blot.Dual luciferase assay was adopted to verify the relationship between OIP5-AS1 and miR-34c-5p.Results Compared with A549 cells,the expression of OIP5-AS1 was significantly up-regulated in A549R cells (1.97±0.11 vs.1.01±0.05,P＜0.05),whereas the expression of miR-34c-5p was remarkably down-regulated (0.43±0.02 vs.1.02±0.06,P＜0.05).The expression levels of p-Chk2 and p-ATM proteins in A549R cells in the silencing OIP5-AS1 +6Gy group were significantly lower (0.43±0.03 vs.1.39±0.15,0.51 ±0.0 5 vs.1.21 ± 0.11,both P＜0.05),whereas the apoptotic rate was significantly higher than those in the silencing control + 6Gy group [(13.29± 1.25)％ vs.(28.47± 2.31)％,P＜0.05)].The expression levels of p-Chk2 and p-ATM proteins in A549 cells in overexpressing OIP5-AS1+6 Gy group were significantly higher than those in overexpression control+6 Gy group (1.23±0.13 vs.0.75±0.06,1.08±0.11 vs.0.59± 0.04,both P＜0.05).Inhibiting miR-34c-5p expression reversed the effect of silencing OIP5-AS1 on survival fraction of A549R cells (SER =1.42).OIP5-AS1 negatively regulated the expression of miR-34c-5p.Conclusion Silencing OIP5-AS1 enhances the radiosensitivity of radiation-resistant A549 cells by up-regulating the expression of miR-34c-5p,providing a potential target for radiotherapy of NSCLC cells.

Silencing LncRNA OIP5-AS1 increases radiosensitivity of non-small cell lung cancer A549 cell line by up-regulating miR-34c-5p expression / 中华放射肿瘤学杂志

Objective@#To investigate the effect of LncRNA OIP5-AS1 on radiosensitivity of non-small cell lung cancer (NSCLC) cells and its mechanism.@*Methods@#The radiation-resistant cell A549R was established by using A549 cells irradiated by X-ray 6Gy in 5 fractions. The expression levels of OIP5-AS1 and miR-34c-5p in A549 and A549R cells were detected by qRT-PCR. OIP5-AS1 inhibitor or miR-34c-5p mimetic was transfected into A549R cells, or OIP5-AS1 overexpression plasmid was transfected into A549 cells. Cell apoptosis was detected by flow cytometry. Cell radiosensitivity was analyzed by colony formation assay. The expression levels of p-Chk2 and p-ATM proteins were measured by Western blot. Dual luciferase assay was adopted to verify the relationship between OIP5-AS1 and miR-34c-5p.@*Results@#Compared with A549 cells, the expression of OIP5-AS1 was significantly up-regulated in A549R cells (1.97±0.11 vs.1.01±0.05, P<0.05), whereas the expression of miR-34c-5p was remarkably down-regulated (0.43±0.02 vs.1.02±0.06, P<0.05). The expression levels of p-Chk2 and p-ATM proteins in A549R cells in the silencing OIP5-AS1+ 6Gy group were significantly lower (0.43±0.03 vs.1.39±0.15, 0.51±0.0 5 vs.1.21± 0.11, both P<0.05), whereas the apoptotic rate was significantly higher than those in the silencing control+ 6Gy group [(13.29±1.25)% vs. (28.47±2.31)%, P<0.05)]. The expression levels of p-Chk2 and p-ATM proteins in A549 cells in overexpressing OIP5-AS1+ 6Gy group were significantly higher than those in overexpression control+ 6Gy group (1.23±0.13 vs.0.75±0.06, 1.08±0.11 vs.0.59±0.04, both P<0.05). Inhibiting miR-34c-5p expression reversed the effect of silencing OIP5-AS1 on survival fraction of A549R cells (SER=1.42). OIP5-AS1 negatively regulated the expression of miR-34c-5p.@*Conclusion@#Silencing OIP5-AS1 enhances the radiosensitivity of radiation-resistant A549 cells by up-regulating the expression of miR-34c-5p, providing a potential target for radiotherapy of NSCLC cells.

Present treatment situation of hepatocellular carcinoma with extrahepatic metastasis / 中华外科杂志

With the development of diagnostic and screening technologies, the incidence of hepatocellular carcinoma (HCC) with extrahepatic metastasis is increasing. It is a kind of refractory disease with extremely poor prognosis. Currently, there is no standard therapy. The existing guidelines only recommend targeted therapy, systemic chemotherapy or best supportive care for HCC patients with extrahepatic metastasis, but have not mentioned surgical therapy.Several studies have shown that the majority of HCC patients with extrahepatic metastasis died of progressive intrahepatic tumor leading to hepatic failure, but not extrahepatic metastases; and primary tumor resection may have a favorable impact on the prognosis of these patients with resectable primary tumors.Furthermore, the role of resection of metastatic tumors for HCC patients with extrahepatic metastasis remains unclear so far.Majority of experts think that resection of lung metastases has survival benefit when the hepatic lesion is resected or controlled, whereas resection of lymph nodes, bone metastases, adrenal gland lesions, or brain metastases does not prolong survival, which may be recommended when the goal is to relieve symptoms or improve quality of life.Therefore, surgical treatment is important for HCC patients with extrahepatic metastasis, and surgical therapy combined with personalized systemic treatment shows survival benefit for selected patients.

Surgical treatment of liver malignant tumors with extrahepatic metastasis / 中华消化外科杂志

With the development of diagnostic and screening technologies,the incidence of hepatocellular carcinoma (HCC) with extrahepatic metastasis is increasing and surgical rate is also increasing.There is currently no standard of treatment.Four famous experts and their teams in hepatic surgery discussed reasonability of surgical treatment for HCC with extrahepatic metastasis based on clinical experiences.Professor Geng Xiaoping suggested that HCC with extrahepatic metastasis was classified as advanced HCC,however,under the premise of strict control of indications,selective patients undergoing comprehensive treatment combined with surgical procedures could achieve good prognosis.For some rare liver malignancies,active surgical treatment for extrahepatic metastasis based on comprehensive treatment was recommended.Professor Zhou Jian proposed that resection of intrahepatic lesions in HCC with extrahepatic metastasis should be based on the premise of whether to prolong the survival of patients.He advocated choice of individualized treatment and comprehensive treatment of multiple methods to benefit patients' survival.The necessary intrahepatic lesion resection was a positive and feasible treatment strategy.Professor Wang Jie shared the diagnosis and treatment of 2 patients with HCC and extrahepatic metastasis,suggested that primary tumor resection might have a favorable impact on the prognosis of these patients with resectable primary tumors.Therefore,surgical treatment was important for HCC patients with extrahepatic metastasis,and surgical therapy combined with personalized systemic treatment showed survival benefit for selected patients.Professor Zhou Weiping recommended that choosing surgery for HCC with extrahepatic metastasis should be extraordinarily cautious.Priority should be given to improving the survival rate of patients.In the case of effective control or complete necrosis of extrahepatic metastases,hepatic primary tumor resection was still the current mainstream opinion.

Quantitative evaluation of image quality of megavoltage computed tomography for guiding helical tomotherapy / 北京大学学报(医学版)

OBJECTIVE@#To quantitatively analyze image quality of two sets of phantom (CatPhan504 and Cheese) Megavoltage computed tomography (MVCT) images acquired by Helical Tomotherapy with three scanning modes (Fine, Normal and Coarse), and to explore and validate a semi-automatic quality assurance procedure for MVCT images of Helical Tomotherapy.@*METHODS@#On Helical Tomotherapy, CatPan504 and Cheese phantoms were scanned with three pitch levels (Fine, Normal, Coarse: 4 mm, 8 mm, 12 mm/circle) respectively. Pylinac, Matlab and Eclipse were used to calculate and compare spatial resolution, noise level and low contrast resolution of images obtained under three scanning modes respectively. The spatial resolution can be evaluated by the blurring of line-pair CT value in the images of CatPhan504's CTP528 module. The noise level can be evaluated by the integral non-uniformity in the images of Cheese's uniformity module. the low contrast resolution can be evaluated by contrast-to-noise ratio of both phantoms' plug-in module, or visibility of the region of interest (Supra-Slice) in the images of CatPhan504's CTP515 module.@*RESULTS@#Analyses on CatPhan504's line pair module(CTP528 module) showed that the first three line pairs(the gap size are 0.500 cm, 0.250 cm and 0.167 cm respectively) could be clearly observed but blurring began to occur from the fourth line pair(the gap size is 0.125 cm) under Coarse mode. Meanwhile, the first four line pairs were all observable under the Normal and Fine modes. Integral non-integrity index(the value negatively correlated with the noise level) were 0.155 7, 0.136 8 and 0.122 9 for Coarse, Normal and Fine modes respectively. None of the Supra-Slice in CatPhan504's CTP515 module could be observed under three imaging modes. Low contrast contrast-to-noise ratio of Cheese phantom was similar under three modes and the insert visibility exhibited nearly linear growth with the increasing difference between CT average value of the insert material and background.@*CONCLUSION@#Superiority and inferiority of three image modes in terms of the three image quality index was not consistent. Evaluation results above could provide reference for more rational decision on scanning modes selection of helical tomotherapy, which was based on image visualization demands in clinical practice. The proposed method could also provide guidance for similar image quality assessment and periodic quality assurance.

Establishment of enzalutamide-resistant human prostate cancer cell lines and screening of lncRNA and mRNA expression profiles / 中华男科学杂志

Objective@#To establish enzalutamide-resistant human prostate cancer cell lines and screen out the lncRNA and mRNA expression profiles associated with enzalutamide resistance.@*METHODS@#Human prostate cancer cell lines LNCAP and C4-2B were cultured with 10 μmol/L enzalutamide for 6 months in vitro for the establishment of enzalutamide-resistant subclones LNCAP-ENZA and C4-2B-ENZA. The IC50 value and enzalutamide resistance index of each cell line were examined by MTT assay, the expressions of enzalutamide-related genes FL-AR, AR-V7 and HnRNPA1 were determined by Western blot, and the lncRNA and mRNA differential expressions of C4-2B and C4-2B-ENZA were detected by high-throughout lncRNA microarray.@*RESULTS@#Compared with LNCAP and C4-2B, the IC50 values of enzalutamide-resistant subclones LNCAP-ENZA (60.83 μmol/L) and C4-2B-ENZA (88.32 μmol/L) were increased significantly (P < 0.05) and the enzalutamide-resistance indexes of the LNCAP-ENZA and C4-2B-ENZA cells were 4.94 and 4.67, respectively. The expressions of AR-V7 and HnRNPA1 were markedly up-regulated in the LNCAP-ENZA and C4-2B-ENZA cells as compared with those in the LNCAP and C4-2B cells, but that of FL-AR showed no significant change. A total of 1 440 lncRNAs and 1 236 mRNAs were identified as differentially expressed in the C4-2B-ENZA cells.@*CONCLUSIONS@#Enzalutamide -resistant human prostate cancer cell subclones LNCAP-ENZA and C4-2B-ENZA were successfully established and enzalutamide resistance-associated lncRNA and mRNA were identified, which may provide some molecular evidence for the management of enzalutamide-resistant human prostate cancer.

Study of dose distribution of sublingual gland carcinoma treating with 125I radioactive seeds / 中华放射医学与防护杂志

Objective To measure and calculate the dose distribution (tissue absorbed dose) of mouth floor area while using 125I to treat sublingual gland carcinoma.Methods Phantom of head and neck was used to place the 125I radioactive seeds to simulate the sublingual gland carcinoma treatment.125I radioactive seeds of 29.6 and 25.9 MBq per seed were used as two groups,with 31 seeds in each group,and prescribed dose (peripheral matched dose) was 120 Gy.Thermoluminescence dosimetry (TLD) was used to measure the absorbed dose value in the simulated target and adjacent area.Gafchromic Eriochrome Black T (EBT) film was used to draw the dose distribution curve.Results Dose absorbed in the target area,target area center and the adjacent area one centimeter away from target reached 160 Gy,390-500 Gy,and 90-170 Gy,respectively.Dose of the skin ranged from 25 to 81 Gy,dose of mandible ranged from 7.9 to 67 Gy.No radiation cold spot was found.Conclusions 125I seeds could achieve an effective therapeutic dose distribution of the target area for sublingual gland carcinoma.Dose absorbed in the adjacent tissue is under safety limit.The radiation dose at mandible is lower,reducing the possibility of radiation damage to the bone.

Research progress of microRNA in the early diagnosis of lung cancer / 肿瘤研究与临床

microRNA(miRNA)is a group of naturally occurring small non-coding RNA of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level.miRNAs relates closely with the progressive,diagnosis,treatment and prognosis in lung cancer,this article describes the miRNA in the early diagnosis of lung cancer and potential application value to elaborate.

Design and development of the multi-dimensional ultrasonic reconstruction and visualization system / 生物医学工程学杂志

The design and development of multi-dimensional ultrasonic reconstruction and visualization system (MURVS) have been described in the present paper. This system is basically composed of four modules: the data input/output module, image segmentation and arrangement module, multi-dimensional reconstruction module, and the dynamic visualization module. At first, some algorithms used in the system are introduced by the authors, including the AVI segmentation algorithm, three-dimensional interpolation algorithm, and volume rendering algorithms. Then the key questions of techniques to be discussed are: how to design the main modules, how to solve the dynamic visualization problem, and how to implement the system. The experiments indicate that MURVS is able to reconstruct all three-dimensional data fields in one cardiac cycle of a patient within 4 seconds, and dynamically display the motion of the heart. It allows the medical professionals to select different parameters when observing the reconstructed results. This is very helpful for medical professionals to reach more accurate diagnoses of their patients' diseases.

Evaluation of therapeutic effects with intra-operative iodine-125 seed implantation for advanced pancreatic carcinoma / 中华放射肿瘤学杂志

Objective To analyze the clinical effects of internal radiation of iodine-125 seed implantation in the treatment of advanced pancreatic carcinoma.Methods Ten patients with unresectable and advanced pancreatic carcinoma admitted from Sept.2002 to June 2004 were treated by the internal and interstitial radiation using iodine-125 seed implantation. Sex:male 6, female 4. Age: median 60.8(45-81) years. Site by pre-operative CT: pancreatic head 4, body 2 and tail 4. Diameter: 6?cm 3. Pathology: all proved to be pancreatic adenocarcinoma. Staging(UICC 1997): stage Ⅲ 3, IV 7. Pain degree: Ⅲ 3,IV 7. Weight loss: median 5?kg(3-10?kg). Results All patients have been followed for 2-13 months, median 6 months. Survival of 12 months was observed in 1 patient,6 months in 3 patients, 3 months in 4 and 1 month in 2, with an average of 4.6 months. Among the 10 patients, complete response was obtained in 2, partial response in 3, no response in 4, and the other showing PD. The response rate (CR+PR) was 50%. The pain relieving rate was 60%. The seed number conformal rate was 100% by X-ray film, yet that of seed spatial distribution was only 30%. Conclusion Intra-operative internal radiation by iodine-125 seed implantation does show some therapeutic effects for advanced pancreatic carcinoma.Yet,the seed spatial distribution by seed computer treatment planning system does needs further consummate.