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Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.
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Objective:To identify the prevalence of pulmonary micro nodule (PMN) in osteosarcoma, investigate radiologic features of progressive PMN, and provide evidence for early diagnosis of pulmonary metastasis of osteosarcoma.Methods:Electronic articles published in PubMed, EMBASE, Web of Science and the Cochrane Library databases between January 1, 2000, and September 1, 2022, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the prevalence of PMN in osteosarcoma and radiologic features of progressive PMN. Seven high quality studies were finally included in the meta-analysis with evidence level III.Results:The pooled prevalence of PMN in osteosarcoma was 36.0%, 95% CI (14.6%, 57.3%). The pooled progressive rate of PMN was 52.5%, 95% CI (37.7%, 67.2%). As for a specific PMN, it was more likely to progress which had a larger Dmax, HR=2.40, 95% CI (1.06, 5.42), P=0.035. No significant difference was found in number, component, and border. Conclusion:PMN is quite common in patients with osteosarcoma. About half of the patients suffered the progression of PMN, and it is related to several risk factors.
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Objective:To analyze the clinical value of high-frequency color Doppler ultrasound in the detection of axillary lymph node metastasis in breast cancer.Methods:The clinical data of 60 patients with breast cancer who received treatment in Hangzhou Hospital, Zhejiang Medical & Health Group between March 2017 and March 2019 were retrospectively analyzed. Based on pathological results, 34 patients with breast cancer who had axillary lymph node metastasis were included in the observation group, and 26 patients without axillary lymph node metastasis were included in the control group. Both groups of patients underwent high-frequency color Doppler ultrasound examination. Ultrasound image characteristics, distribution of blood flow within the lymph nodes, and grading of blood flow signals were compared between the two groups, and ultrasound diagnosis results were analyzed.Results:Detection rate of cortical thickening, detection rate of lymph node long-diameter to lymph node short-diameter ratio > 2, detection rate of blurred lymph node borders, and detection rate of calcified foci within lymph nodes in the observation group were 55.9% (19/34), 58.8% (20/34), 61.8% (21/34), 52.9% (18/34), respectively, which were significantly higher than those in the control group [11.5% (3/26), 26.9% (7/26), 19.2% (5/26), 7.7% (2/26), χ2 = 12.48, 6.06, 10.85, 13.57, all P < 0.05]. The percentage of peripheral type blood flow distribution in the observation group was significantly higher than that in the control group and the percentage of portal type blood flow distribution in the observation group was significantly lower than that in the control group (both P < 0.05). The percentage of grade 2 blood flow signal in the observation group was significantly lower than that in control group, and the percentage of grade 3 blood flow signal in the observation group was significantly higher than that in the control group (both P < 0.05). The sensitivity, specificity, misdiagnosis rate and missed diagnosis rate of ultrasound in the detection of axillary lymph node metastasis in breast cancer were 88.2% (30/34), 73.1% (19/26), 26.9% (7/26), and 11.8% (4/34), respectively. Conclusion:High-frequency color Doppler ultrasonography in the detection of breast cancer axillary lymph node metastasis has ideal accuracy, and its diagnostic results are of high reference value.
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Pathophysiology is a comprehensive subject, which is very important to cultivate the clinical comprehensive thinking of medical students. Pathophysiology involves a wide range of subjects and contents, and is one of the major and difficult courses in basic medicine. Based on many years of research and practice, we have developed main-line-problem-based learning (ML-PBL). ML-PBL is a diversified teaching mode, including the main line teaching method, clinical case discussion method, and the main line synopsis explaining method. The analysis of application results shows that ML-PBL teaching improves the student performance. Furthermore, ML-PBL is more conducive to cultivating the comprehensive clinical thinking ability, improving the independent learning ability, and fully mobilizing the learning initiative.
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Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
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Objective To compare the effectiveness of Pregabalin given by fixed dose method and flexible dose method on treating central post-stroke pain.Methods Patients with central post-stroke pain were consecutively enrolled and randomized into fixed group and flexible group.The patients in fixed group were given pregabalin 300 mg per day for 8 weeks.The patients in flexible group were given pregabalin as follows:150 mg per day for 2 weeks, 300 mg per day for 2 weeks and 450 mg per day for 4 weeks.The primary outcome was numerical rating scale ( NRS) . The secondary outcomes included adverse effects, hospital anxiety and depression scales ( HADS ) and Athens insomnia scale ( AIS) .Results A total of 132 participants were enrolled with 65 in fixed group and 67 in flexible group from Jul 2009 to Dec 2014.Two patients in fixed group gave up the treatment while 7 patients gave up in flexible group though no significant difference was observed.Finally, 63 patients in fixed group and 60 patients in flexible group were included into analysis.There was no significant difference on gender, age, medical history between two groups. Compared with baseline, the NRS、HADS-A、HADS-D and AIS score were significantly decreased ( all P<0.05 ) .However, there was no significant difference of these scores between the two groups. Conclusion Two regimens of pregabalin showed the similar efficiency and safety to treat CPSP, however, fixed dose seemed to be more acceptable.
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Objective To evaluate the relation of appearance of contrast-enhanced ultrasonography (CEUS) to Ki 67 and C-erbB-2 in breast invasive ductal carcinoma and ductal carcinoma in situ.Methods The appearance of CEUS in 29 patients with breast invasive ductal carcinoma and 12 patients with ductal carcinoma in situ,which was diagnosed by surgery or biopsy,was analysed retrospectively.The Ki-67 and CerbB-2 were measured by immunohistochemical test.The relation of the above two factors to appearance of contrast ultrasonography was analysed.Results The positive rate of Ki-67 was 68.97％ (20/29) in patients with breast invasive ductal carcinoma and 16.67％ (2/12) in patients with ductal carcinoma in situ.The positive rate of C-erbB-2 was 48.2％ (14/29) in patients with breast invasive ductal carcinoma and 42.6％ (5/12) in patients with ductal carcinoma in situ.The masses had a common appearance of high enhance in patients with breast invasive ductal carcinoma and ductal carcinoma in situ,which was not correlated to C-erbB-2.The Ki-67 was significantly higher in patients with ductal carcinoma in situ than that in patients with breast invasive ductal carcinoma,the appearance of CEUS was correlated to Ki 67.Conclusions The features of micro-vessels by CEUS were correlated to Ki-67 in patients with breast invasive ductal carcinoma and ductal carcinoma in situ.