Efficacy of low frequency pulsed electromagnetic field therapy in treatment of peritumoral edema of glioma / 上海预防医学

Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.

Efficacy of low frequency pulsed electromagnetic field therapy in treatment of peritumoral edema of glioma / 上海预防医学

Objective To evaluate the efficacy of low frequency pulsed electromagnetic field (LFPEMF) on peritumoral edema in patients with glioma, providing a theoretical basis for clinical treatment of peritumoral edema. Methods This study included 32 patients with recurrent cerebral glioma with peritumoral edema after the operation of glioma in department of glioma, Beijing Shijitan Hospital, Capital Medical University from March 2017 to December 2018.The period of LFPEMF treatment was 10-14 days.The clinical symptoms related to brain edema were recorded before and after treatment.The National Institutes of Health Stroke Scale (National Institute of health stroke scale, NIHSS), Karnofsky quality of life score (KPS), brain edema and tumor range in cranial MRI, T lymphocyte subgroup CD4+/CD8+, superoxide dismutase (SOD) were recorded.The SPSS21.0 statistical analysis software was used to carry out analysis by using self controlled study.P < 0.05 was statistically significant. Results After the treatment of LFPEMF, the results showed that LFPEMF was effective in 25 patients, invalid in 7 patients, and the total effective percentage was 78.13%.The area of brain edema was significantly improved after using LFPEMF(P < 0.05).There was no significant improvement in the area of brain tumor after using LFPEMF therapy (P>0.05).KPS and NIHSS scores improved significantly after using LFPEMF (P < 0.05). Conclusion In the patients with peritumoral edema of glioma, the application of LFPEMF in the patients′ Yongquan point and Lao Gong point can reduce peritumoral edema, and improve clinical symptoms.

Antibacterial activity of bacillomycin D-like compounds isolated from Bacillus amyloliquefaciens HAB-2 against Burkholderia pseudomallei

Objective: To investigate the inhibitory effect on Burkholderia pseudomallei (B. pseudomallei) strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2. Methods: The antibacterial effect of bacillomycin DC on B. pseudomallei was determined using the disk diffusion method. The minimum inhibitory concentrations were evaluated by microdilution assay. In addition, transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of MexB, OprD2, and qnrS genes. Results: Bacillomycin DC produced an inhibition zone against B. pseudomallei with minimum inhibitory concentration values of 12.5 μg/mL 24 h after treatment and 50 μg/mL at 48 and 72 h. Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage. Quantitative real-time polymerase chain reaction analysis showed low expression of MexB, OprD2 and qnrS genes. Conclusions: Bacillomycin DC inhibits the growth of B. pseudomallei and can be a new candidate for antimicrobial agents of B. pseudomallei. Rajaofera Mamy 1 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Kang Xun 2 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Jin Peng-Fei 3 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Chen Xin 4 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Li Chen-Chu 5 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Yin Li 6 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Liu Lin 7 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Sun Qing-Hui 8 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Zhang Nan 9 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Chen Chui-Zhe 10 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan He Na 11 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Xia Qian-Feng 12 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Miao Wei-Guo 13 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Kung CT, Lee CH, Li CJ, Lu HI, Ko SF, Liu JW. 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Antibacterial activity of bacillomycin D-like compounds isolated from Bacillus amyloliquefaciens HAB-2 against Burkholderia pseudomallei

Objective: To investigate the inhibitory effect on Burkholderia pseudomallei (B. pseudomallei) strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2. Methods: The antibacterial effect of bacillomycin DC on B. pseudomallei was determined using the disk diffusion method. The minimum inhibitory concentrations were evaluated by microdilution assay. In addition, transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of MexB, OprD2, and qnrS genes. Results: Bacillomycin DC produced an inhibition zone against B. pseudomallei with minimum inhibitory concentration values of 12.5 μg/mL 24 h after treatment and 50 μg/mL at 48 and 72 h. Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage. Quantitative real-time polymerase chain reaction analysis showed low expression of MexB, OprD2 and qnrS genes. Conclusions: Bacillomycin DC inhibits the growth of B. pseudomallei and can be a new candidate for antimicrobial agents of B. pseudomallei.

Features and therapeutic potential of T-cell receptors in high-grade glioma / 中华医学杂志(英文版)

Background@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*Methods@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*Results@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*Conclusions@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

Efficacy and Safety of Crizotinib in Advanced or Recurrent ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.@*METHODS@#Three methods were used to screen patients with advanced or recurrent NSCLC harboring ALK gene fusion/translocation. The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid. The objective response rate (ORR), progression-free survival (PFS) and safety were evaluated.@*RESULTS@#A total of 226 patients were screened, 39 of whom had ALK fusion or translocation, and 37 were enrolled in the study. 35 patients were evaluated for objective response, ORR was 70.3%, and disease control rate (DCR) was 94.6%, and median PFS was 11.8 mon. The main adverse reactions were elevated transaminase (Grade 1, 91.7%), elevated transaminases (Grade 2, 23.4%), nausea (Grade 1, 75.6%), anemia (Grade 1-2, 62.3%), visual impairment (Grade 1, 21.8%), weight loss (Grade 1, 31.4%), pneumonia (Grade 2, 3.5%).@*CONCLUSIONS@#Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation. It is highly effective and well tolerated.

Clinical Characteristics, Treatment and Prognosis of 47 Non-small Cell Lung Cancer with Neuroendocrine Differentiation Patients / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED) was a new pathologic type and uncommon in clinics. The aim of this study is to observe the relationship between clinical pathologic characteristics, imagination, biological behavior and prognosis in NSCLC-NED.@*METHODS@#The clinical data of 47 patients with NSCLC-NED admitted from January 2009 to November 2017 in the Fifth Medical Center of General Hospital of People's Liberation Army were collected. The demographic data and imaging characteristics were summarized. Pathological features, treatment and prognosis, analysis of the correlation between different factors and prognosis.@*RESULTS@#Of the 47 patients with NSCLC-NED, the median age was 61 years (45 years-78 years), 38 males and 9 females; 37 were poorly differentiated cancer with NED, and 10 were middle differentiated cancer with NED; 2 cases of driving gene positive (1 case of EGFR sensitive mutation, 1 case of ALK fusion), objective response rate (ORR) of first-line chemotherapy was 34.5%, and median progression-free survival (PFS) was 4 months; the median overall survival (OS) was 11 months, and only 2 cases (4.2%, 2/47) of OS were over 2 years.@*CONCLUSIONS@#NSCLC-NED is different from simple NSCLC or pulmonary neuroendocrine tumors. Males, ≤70 years old, severely smoking, and patients with lower tumor differentiation often have NED, and most of them are stage IV. This type of patient-driven gene positive proportion is lower than the general adenocarcinoma population, less sensitive to chemotherapy, and the overall survival is shorter, indicating a poor prognosis.

Features and therapeutic potential of T-cell receptors in high-grade glioma / 中华医学杂志(英文版)

BACKGROUND@#Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of high-grade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.@*METHODS@#During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.@*RESULTS@#The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.@*CONCLUSIONS@#HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

Efficacy and influence factors of concurrent radiotherapy and chemotherapy for high-grade brainstem glioma / 中国肿瘤临床

Objective: To perform a retrospective analysis of the prognosis and influence factors of radiotherapy concurrent with che-motherapy and adjuvant temozolomide therapy in adult patients with high-grade brainstem glioma. Methods: Twenty-nine patients with pathological diagnosis of high-grade glioma (World Health Organization [WHO] Ⅲ and Ⅳ) from June 2012 to December 2013 were eligible for inclusion in the analysis. Demographic and clinical characteristics including age, gender, the time from morbidity to operation, the size of the lesion, the method of operation, the Karnofsky Performance Status (KPS) score, and the pathological grade were examined. The significance of related prognostic factors was evaluated via univariate and multivariate Logistic regression analy-sis. A P-value of<0.05 was considered to be statistically significant. Results: The median overall survival (OS) was 11.5 months. Univari-ate analysis showed that low WHO grade index was associated with better outcome (P<0.05). Multivariate analysis suggested that high KPS score (>60) and low WHO grade were associated with better survival. Conclusions: In this study, low pathological grade and high KPS score were independently associated with better survival among patients with high-grade brainstem glioma.

Bacillomycin D-like compounds isolated from Bacillus amyloliquefaciens HAB-2 are effective against Burkholderia pseudomallei

Background:Burkholderia pseudomallei (Bp) is a gram-negative environmental bacterium that causes melioidosis. It has high mortality and relapse rates regardless of powerful antibiotic therapy. Bacterial pathogens display versatile gene expression to adapt to changing surroundings, especially when they are infected by drugs. A cyclic lipopeptide was isolated from Bacillus amyloliquefaciens HAB-2, which is a bacillomycin D-like compound, named as bacillomycin DC. It is a potent fungicide against Colletotrichum gloeosporioides Penz.Methods:We used this kind of bacillomycin DC to be inhibitor of Bp and in order to find out how does it infect the bacterial pathogens. We observed the morphological changes under transmission electron microscope (TEM) and scanning electron microscopy (SEM) when BP is in the minimum inhibitory concentration (MIC) of ceftazidime and bacillomycin DC. Then we used quantificationgene Real-Time PCR (qRT-PCR) to measure the expression of three drug-assistant genes including MexB, qnrS and oprD2, respectively.Results:Bacillomycin DC treatment caused changes in the shape and microstructure, and the bacterial outer membrane were damaged, the leakage of the cell were observed. The expression level of mexb gene was not high until 72h after ceftazidime and bacillomycin DC treatment. Both ceftazidime and bacillomycin DC caused high expression of oprD2, but higher expression level proves that the DC works more efficiently and quickly. Bacillomycin DC increased the expresssion level of bacteria qnrS gene in 24 h, which proved this compound injured the DNA helicase and topoisomerase of the bacteria in a short time. The results showed that the bacillomycin DC had better inhibitory effects. We also found out that different mechanism of action between ceftazidime and bacillomycin DC.Conclusion:The bacillomycin DC makes bacterial pathogen display more oprD2 and qnrS, which respectively means bacterial pathogen are sensitive to the bacillomycin DC and its DNA gyrase are injured. In short, our study showed for the first time that bacillomycin DC can inhibit Bp in a short time.

The prospect of chlorogenic acid in the treatment of glioma / 中国肿瘤临床

As a common primary intracranial tumor,malignant glioma accounts for 81% of all central nervous system malignancies.Af-ter standard treatment,such as surgery combined with external radiotherapy and chemotherapy,glioblastoma patients'survival is on-ly 14.4 months.Hence,the traditional treatment is difficult to meet patients'needs of survival and life quality.In recent years,chloro-genic acid(CGA),as plant extract polyphenols,has received widespread attention.Its antitumor properties,through its effects on the immune system,anti-oxidation properties,cell cycle regulation,and inhibition of tumor cell metastasis and invasion,have been exten-sively studied.This article will discuss the mechanisms involved in glioma treatment,synergism with other drugs,and metabolism in the human body,to provide a reference for the application of CGA in the treatment of the condition.

Clinical characteristics of 15 glioma cases with leptomeninges and spinal cord metastases / 中国肿瘤临床

Objective:To retrospectively analyze and summarize the clinical characteristics of 15 glioma cases that led to leptomenin-ges and spinal cord metastases in Department of Glioma, Beijing Shijitan Hospital, Capital Medical University since 2011. Methods:A total of 15 cases were considered, including 5 patients with World Health Organization gradeⅡ, 6 patients with gradeⅢ, and 4 pa-tients with gradeⅣ. One patient had a tumor at the brain stem, two patients had tumors at the spinal cords, and the other patients had tumors at the hemispheres. One case received biopsy, 4 cases received subtotal resection, and 10 cases received complete resec-tion. Results: Symptoms included low back pain, sensory and motor dysfunction, incontinence, and seizures. After the metastases spread to the cerebrospinal region, patients were treated with chemotherapy, whole spine radiotherapy, intrathecal chemotherapy, and target therapy. The median time of leptomeninges and spinal cord metastasis dissemination appearance was 10 months (1.5-80 months) since surgery. The median overall survival time of the 15 patients was 20 months (9-83 months), and the median survival time was 6 months (2-48 months) after leptomeninges and spinal cord metastases. Conclusion:The prognosis of glioma patients with lepto-meninges and spinal cord metastases was poor, and a proportion of the patients who received appropriate treatment might have a better survival.

PhaseⅠStudy of nimotuzumab combined with postoperative chemoradiotherapy in Chinese patients with malignant glioma / 中国肿瘤临床

Objective:The poor prognosis of patients with malignant gliomas (MG) has led to the search for new therapeutic strat-egies. Recently, nimotuzumab has been studied as a new anti-EGFR-receptor humanized monoclonal antibody in patients with MG, who showed improvement of outcome and good tolerability. We conducted phase I of our study to determine the toxicity, tolerated dose, and clinical feasibility of nimotuzumab in combination with concurrent chemoradiotherapy for Chinese MG patients after surgical resection. Methods:Patients with pathologically proven grades 3 and 4 glioma were enrolled in the study. The protocol included infu-sions of nimotuzumab plus standard Stupp schedule (postoperative radiotherapy in a total dose of 60 Gy in combination with daily te-mozolomide). Patients received 6 weekly infusions of nimotuzumab at three levels (100, 200, and 400 mg/week). If none of the first three patients enrolled at a dose level experienced dose-limiting toxicity (DLT), the dose was increased, as appropriate. If DLT was ob-served, another three patients were added to the dose level. Results:Nine patients with MG were enrolled, including 7 with grade 3 MG and 2 with glioblastoma. The treatment was well tolerated, and no evidence of grade 3 or 4 adverse events was detected, even at the highest level (400 mg/week). Grade 1 or 2 myelosuppression was the most common toxicity. Three months after treatment, stable dis-ease occurred in 5 patients, whereas progression disease was observed in 4 patients. Conclusion:Nimotuzumab combined with concur-rent chemoradiotherapy was associated with mild toxicity in Chinese MG patients.