Advances in early biomarkers of anthracyclines related to cardiotoxicity / 实用肿瘤学杂志

Anthracyclines are one of the widely used anti-tumor drugs in clinical practice.Its dose-related cardiotoxicity can affect the quality of life and survival rate of cancer patients,so early identification of anthracycline related cardiotoxicity is particu-larly important.This article provides a review of the research progress on early biomarkers of anthracycline related cardiotoxicity.

Investigation of high-incidence skin diseases in the army and its application in the curriculum integration of skin diseases / 中华医学教育探索杂志

Taking the curriculum integration of skin diseases as an example, this paper summarizes the skin diseases with high incidence in the army such as acne, tinea pedis, warts, folliculitis, corns and calluses, sunburns, etc. The results have been applied to the integration of the skin disease curriculum in Air Force Medical University. During the course integration process, we integrated the courses of dermatology, plastic surgery and burn surgery together, and simplified the teaching content according to the "organ-system" orientation and features of military medical university. In the teaching process, the PBL teaching method was used to guide the students to discuss with the problems. At the end of the course, the students were assessed by tests, and the satisfaction evaluation were carried out. The results showed that the application of high incidence of skin diseases in the army in curriculum integration can help improve the teaching effect and the satisfaction of students, which will provide a certain reference for the curriculum integration reform of military medical universities.

Minimally invasive treatment for osteonecrosis of the femoral head in ARCO stage Ⅱ and Ⅲ with bioceramic system / 中国修复重建外科杂志

Objective: To perfect the theory system of minimally invasive treatment for osteonecrosis of the femoral head (ONFH) with β tricalcium phosphate (β-TCP) bioceramic system and evaluate the effectiveness. Methods: Eighteen New Zealand white rabbits aged 7-8 months were used to establish an animal model to verify the vascularization of porous β-TCP bioceramic rods. Micro-CT based three-dimensional reconstruction and fluorescence imaging were used to display the new blood vessels at 4, 8, and 12 weeks after operation. The inserting depth, number and diameter of vessels in the encapsulated area were analyzed. Nine pig femoral specimens were randomly divided into 3 groups ( n=3): group A was normal femur; group B had cavity (core decompression channel+spherical bone defect in femoral head); in group C, mixed bioceramic granules were implanted to fill the defect in femoral head, and porous β-TCP bioceramic rod was implanted into decompression channel. The stiffness and yield load of specimens were analyzed by biomechanical test. A multicenter retrospective study was conducted to analyze 200 patients (232 hips) with femoral head necrosis treated with bioceramic system in 7 hospitals in China between January 2012 and July 2018. There were 145 males and 55 females, with an average age of 42 years (range, 17-76 years). According to the Association Research Circulation Osseous (ARCO) stage, 150 hips were in stage Ⅱ and 82 hips in stage Ⅲ. Postoperative imaging assessment was carried out regularly, and hip function was evaluated by Harris score. The effectiveness of ARCO stage Ⅱ and Ⅲ was also compared. Results: Animal experiments showed that blood vessels could grow into the encapsulated area and penetrate it at 12 weeks. The inserting depth, number and diameter of blood vessels in the encapsulated area gradually increased, and there was significant difference between different time points ( P<0.05). Biomechanical tests showed that the stiffness and yield load of specimens in groups B and C were significantly lower than those in group A, while the yield load in group B were significantly lower than that in group C ( P<0.05). The stiffness in group C was restored to 41.52%±3.96% in group A, and the yield load was restored to 46.14%±7.85%. Clinical study showed that 200 patients were followed up 6-73 months, with an average of 22.7 months. At last follow-up, 12 patients (16 hips) underwent total hip arthroplasty, and the hip survival rate was 93.10%. According to the imaging evaluation, 184 hips (79.31%) were stable and 48 (20.69%) were worse. Harris score (79.3±17.3) was significantly higher than that before operation (57.3±12.0) ( t=18.600, P=0.000). The excellent rate of hip function was 64.22% (149/232). The survival rate of hip joint, imaging score and Harris score of patients in ARCO stage Ⅱ were better than those in ARCO stage Ⅲ ( P<0.05). Conclusion: β-TCP bioceramic system can guide the abundant blood supply of greater trochanter and femoral neck to the femoral head to promote repair; it can partly restore the mechanical properties of the femoral head and neck in the early stage, providing a new minimally invasive hip-preserving method for patients with ONFH, especially for those in early stage.

Clinical significance of peripheral blood circulating tumor cells detection in osteosarcoma patients / 中华骨科杂志

Objective To discuss the correlations amongst the count,molecular and clinicopathological characteristics of circulating tumor cells (CTCs),and the feasibility of using CTC as an aid to judge the metastasis of osteosarcoma,evaluate the therapeutic effect,and predict the prognosis of patients.Methods Retrospective analysis of 30 patients with newly diagnosed osteosarcoma diagnosed from January 2015 to June 2016,there were 17 males and 13 females.The average age was 13.77±4.31 years old (ranged from 7 to 21 years).There were 21 cases of Ennecking stage Ⅱ,including 2 cases of ⅡA,19 cases of ⅡB,and 9 cases of Ennecking Ⅲ.Peripheral blood of all patients was obtained and processed using CanPatrolTM System at baseline,pre-and post-operation.Multiplex RNA-in situ hybridization (RNA-ISH) assay was used to characterize the molecular markers.Combined with clinical data,the relationship between peripheral blood CTC counts,count changes,molecular characteristics,tumor metastasis,chemotherapy effects,and prognosis of patients with osteosarcoma was analyzed and compared.Results The CTC count in peripheral blood was 10.44±5.70 in Ennecking stage Ⅲ patients and 4.76±3.56 in stage Ⅱ patients.The increase or decrease in CTC counts was associated with good or poor neoadjuvant chemotherapy (P=0.002).In patients with good chemotherapy effect,the CTC count in peripheral blood was decreased after chemotherapy.The mean progression-free survival time was 11.85±4.93 months for patients with CTC number ≥7,and the average progression-free survival time was 15.53±4.09 months for patients with CTC number ＜ 7 (P=0.012).The proportion of interstitial CTC in Ennecking stage Ⅲ was 40.42％,which was higher than that of Ennecking ⅡB stage 23.00％.The difference was statistically significant (P=0.010).The positive rate of metastasis-associated gene 1 (MTA1) in interstitial CTC was 85.50％,and the positive rate of other types of CTC was 66.67％.The difference was statistically significant (P=0.000).Conclusion The counting and typing of peripheral blood CTC in osteosarcoma patients can be used as a complement to the commonly used imaging examinations,and they can play an auxiliary role in judging tumor metastasis,curative effect observation and prediction of poor prognosis.

Analysis of risk factors for recurrence of spinal giant cell tumor / 中华骨科杂志

Objective To investigate the factors related to the local recurrence of spine giant cell tumor (GCT) after surgical treatment and provide a reference for the treatment.Methods A retrospective analysis of GCT of the spine from January 2000 to June 2016 was conducted.A total of 73 patients with GCT of the spine who underwent surgical treatment in Giant Cell Tumor Team of China (GTOC) were collected,including 29 males and 44 females.The average age was 33.73±11.34 years (range:13-60 years).Clinical characteristics including gender,age,history of recurrence,tumor position,Ennecking stage,Frankel score,clinical symptoms,surgery procedures,surgical approach,preoperative selective artery embolism (PAE),radiotherapy and bisphosphonate treatment history are collected.The correlation between the factors and tumor recurrence were analyzed by single factor analysis and multiple-factor logistic regression.Results The mean follow-up time was 61.81 ±53.21 months (range:4-210 months).Surgical procedures,bisphosphonate treatment,history of recurrence and radiotherapy were found significant correlation with tumor recurrence by single factor analysis.The result of multiple-factor logistic regression showed that surgical procedures (P=0.026) and bisphosphonate treatment (P=0.017) were independent risk factors for tumor recurrence.Conclusion Total spondylectomy and bisphosphonate treatment could significantly reduce the recurrence rate of GCT of the spine.

Detection and clinical significance of circulating tumor cells in osteosarcoma using immunofluorescence combined with in situ hybridization / 中华肿瘤杂志

Objective@#To investigate the clinical significance of detection of circulating tumor cells (CTCs) in peripheral blood from patients with osteosarcoma (OS) using the iFISH (immunofluorescence and fluorescence in situ hybridization) method.@*Methods@#The live cells recovery rate of immune-magnetic beads was evaluated by live-cell fluorescent tracer technology. The expression of CD45 and CK18 on the cell surface of HOS and HepG2 cells was measured by flow cytometry. And the chromosome aneuploidy was detected by centromeric FISH probe CEP8. Subsequently, 23 OS patients were enrolled and divided into two groups, relapse or metastasis group and primary group. And the prognostic significance of CTCs numbers was analyzed.@*Results@#The live cells recovery rate of immune-magnetic beads was higher than 90%. The flow cytometry results showed that HOS cells were double negative for the surface biomarkers of CD45 and CK18. In addition, the FISH-CEP8 signal abnormality rate were 96.5% in HOS cells. Thus, CTC was identified using the criteria as follows: the cells with CEP8-positive signal >2 accounted for more than 96.5% of the total cells, of which the cells with >3 positive signal were more than 65.0%. Among the enrolled patients, 19 patients had detectable CTCs in the peripheral blood. The CTCs numbers in the relapse or metastasis group and primary group were 2.846±1.281 and 1.400±1.506, respectively. The results showed that the CTCs in patients with recurrence or metastasis were significantly higher than those in primary patients (P=0.021).@*Conclusions@#To our knowledge, this is the first evidence of existence of CTCs in OS patients. The CTCs numbers were positively associated with disease progression and poor prognosis. These results may provide a potential prognostic tool for monitoring metastasis and recurrence in OS patients.@*Trial registration@#Chinese Clinical Trial Registry, ChiCTR-OOC-15005925

Efficacy of low-frequency rTMS to the right frontal cortex for depression:a meta-analysis / 中国神经精神疾病杂志

Objective To systematically assess the efficacy of the low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right frontal cortex for depression. Methods Clinical randomized controlled trials (RCT) studies about low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) for depression were collected from database such as PubMed, SCI, CBM, CNKI, and VIP. The meta-analysis using the software of RevMan 5.2 was conducted to com?pare the response rate of low-frequency rTMS to the right DLPFC with sham stimulation and high-frequency rTMS to the left DLPFC, respectively. Results Nine RCT studies with 156 patients in low-frequency rTMS group and 162 patients in sham stimulation group were included. Meta-analysis showed that low-frequency rTMS to the right DLPFC significantly improved response rate compared with sham stimulation(RR=2.15,95%CI:1.57~2.95,P<0.01). Eleven RCT studies with 178 patients in low-frequency rTMS group and 200 patients in high-frequency group were included. There was no significant difference in response rate between the two groups(RR=0.80,95%CI:0.63~1.02,P=0.07). Conclusion The efficacy of low-frequency rTMS to the right frontal cortex for depression is significant but the efficacy is not superior in comparison with the high-frequency rTMS to left DLPFC.

Mutational analysis of candidate genes in a Chinese pedigree with dominantly inherited auditory neuropathy / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Three genes including the OTOF, the DFNB59 and the DIAPH3 have been implicated previously in human non-syndromic auditory neuropathy. In this study, we aim to investigate whether DIAPH3 gene or the known deafness loci of 25 cloned autosomal dominant deafness (DFNA) genes contribute to the nonsyndromic hearing loss of a Chinese pedigree with dominantly inherited auditory neuropathy (AN).@*METHOD@#Nine members of the kernal pedigree in this family were selected. Genomic DNA was isolated from the peripheral leukocytes of the subjects using the Puregene DNA Isolation Kits. Firstly, the 5'UTR of DIAPH3 gene was PCR amplified in all subjects. Then, the DNA fragments spanning the entire coding regions of DIAPH3, GJB2 and GJB3 genes, and 50 exons in other 23 cloned DFNA genes were amplified using specific primers. Each fragment was purified and analyzed by direct sequencing. The resultant sequence data were compared with the standard sequence to identify deafness-associated mutations.@*RESULT@#PCR amplifications were successfully conducted. We failed to detect the presence either of c. --172G > A mutation in the 5'UTR that have been reported, or any other deafness-associated mutations in the whole DIAPH3 gene, by sequence analysis. We also did not find any known deafness-causing mutations among the 25 cloned DFNA genes.@*CONCLUSION@#The DIAPH3 gene, and the known deafness loci of 25 cloned DFNA genes seem not contribute to the pathogenesis of this Chinese AN family in this study, which suggesting new gene(s) involvement.

Mutation analysis of mitochondrial 12S rRNA gene G709A in a maternally inherited pedigree with non-syndromic deafness / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of mitochondrial DNA mutations with inherited deafness in a maternally inherited pedigree with non-syndromic deafness.</p><p><b>METHODS</b>The diagnosis was validated by hearing tests. Blood samples were collected from 18 maternal members of the family and 53 controls including 6 paternal members, 7 spouses and 40 unrelated individuals. DNA was extracted from the leukocytes in blood samples. The gene fragments of mitochondrial DNA 12S rRNA, tRNA(Ser(UCN)) and GJB2 gene were amplified by polymerase chain reaction(PCR). PCR products were analyzed by sequencing. Computerized 12S rRNA secondary structure modeling was carried out to characterize the mutation found in the family.</p><p><b>RESULTS</b>A novel mitochondrial DNA 12S rRNA 709 G to A transition was detected from all maternal members including 8 patients with hearing loss and other 10 symptom-free maternal members. Non-maternal members and other controls did not carry this mutation. In addition, the tRNA(Ser(UCN))A7445G, 12S rRNA A1555G and GJB2 gene mutations were not observed in the study. Computerized modeling showed that this mutation changed the eighth and ninth loop-stem structure of the 12S rRNA secondary structure.</p><p><b>CONCLUSION</b>In this family, 8 deaf patients carried the mitochondrial DNA 12S rRNA 709 G to A mutation, which is highly conservative in healthy adults. It was confirmed that the mitochondrial DNA 12S rRNA gene G709A was associated with non-syndromic inherited hearing loss. The other 10 maternal members carried the mutation, but they did not suffer from deafness, which might suggest that the G709A mutation may cause hearing impairment in combination with a synergistic effect of some other nuclear modifier genes.</p>

Sequence analysis of DFNB59 gene in a Chinese family with dominantly inherited auditory neuropathy / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate if the DFNB59 gene contributes to the hearing loss of a Chinese pedigree with dominantly inherited auditory neuropathy (AN).@*METHOD@#Nine members in four generations of the family were selected for this study. Genomic DNA was isolated from the peripheral leukocytes of the patients using the pure gene DNA isolation kits. Firstly, the subjects DNA fragment was PCR amplified using specific primers corresponding to exon 2 and 4 of the DFNB59 gene. Each fragment was purified and subsequently analyzed by direct sequencing in an applied biosystems 3730 automated DNA sequencer. The whole coding sequence of DFNB59 gene of one family patient were then PCR amplified and submitted for sequence analysis as described above. The resultant sequence data were compared with the standard sequence to identify deafness-associated mutations.@*RESULT@#PCR amplifications were successfully conducted in all the subjects. We failed to detect the presence either of mutations T54I and R183W in the exon 2 and exon 4 that have been reported, or any other deafness-associated mutations in the whole DFNB59 gene, by sequence analysis.@*CONCLUSION@#The DFNB59 gene seems not contribute to the pathogenesis of this Chinese AN family, which suggesting new gene(s) involvement.