Correlation between the setting of gating window width and setup accuracy in left breast cancer radiotherapy based on deep inspiration breath hold.

Personalized precision irradiation of patients with left-sided breast cancer is possible by examining the setup errors of 3- and 4-mm gated window widths for those treated with deep inspiration breath-hold (DIBH) treatment. An observational study was performed via a retrospective analysis of 250 cone-beam computed tomography (CBCT) images of 60 left-breast cancer patients who underwent whole-breast radiotherapy with the DIBH technique between January 2021 and 2022 at our hospital. Among them, 30 patients had a gated window width of 3 mm, while the remaining 30 had a gated window width of 4 mm; both groups received radiotherapy using DIBH technology. All patients underwent CBCT scans once a week, and the setup errors in the left-right (x-axis), inferior-superior (y-axis), and anterior-posterior (z-axis) directions were recorded. The clinical-to-planning target volume (CTV-PTV) margins of the two gating windows were calculated using established methods. The setup error in the Y direction was 1.69 ± 1.33 mm for the 3-mm - wide gated window and 2.42 ± 3.02 mm for the 4-mm - wide gated window. The two groups had statistically significant differences in the overall mean setup error (Dif 0.7, 95% CI 0.15-1.31, t = 2.48, p= 0.014). The Z-direction setup error was 2.32 ± 2.12 mm for the 3-mm - wide gated window and 3.15 ± 3.34 mm for the 4-mm - wide gated window. The overall mean setup error was statistically significant between the two groups (Dif 0.8, 95% CI 0.13-1.53, t= 2.34, p = 0.020). There was no significant difference in the X-direction setup error (p > 0.05). Therefore, the CTV-PTV margin values for a 3-mm gated window width in the X, Y, and Z directions are 5.51, 5.15, and 7.28 mm, respectively; those for a 4-mm gated window width in the X, Y, and Z directions are 5.52, 8.16, and 10.21 mm, respectively. The setup errors of the 3-mm - wide gating window are smaller than those of the 4-mm - wide gating window in the three dimensions. Therefore, when the patient's respiratory gating window width is reduced, the margin values of CTV-PTV can be reduced to increase the distance between the PTV and the organs at risk (OARs), which ensures adequate space for the dose to decrease, resulting in lower dose exposure to the OARs (heart, lungs, etc.), thus sparing the OARs from further damage. However, some patients with poor pulmonary function or unstable breathing amplitudes must be treated with a slightly larger gating window. Therefore, this study lays a theoretical basis for personalized precision radiotherapy, which can save time and reduce manpower in the delivery of clinical treatment to a certain extent. Another potential benefit of this work is to bring awareness to the potential implications of a slightly larger gating window during treatment without considering the resulting dosimetric impact.

Effects of METTL14 regulating CCNL2 on the activity and invasion of breast cancer cells / 中华内分泌外科杂志

Objective:To investigate the effect of methyltransferase like 14 (METTL14) on the proliferation and invasion of breast cancer (BC) cells by regulating cyclin L2 (Cyclin L2, CCNL2) through m6A modification.Methods:Cancer tissues and paracancerous tissues of BC patients in Yantaishan hospital were collected from Aug. 2018 to Feb. 2020. The expression levels of m6A, METTL14 and CCNL2 in tissues were detected by high performance liquid chromatography/mass spectrometry (HPLC/MS) and qRT-PCR. Dual-luciferase reporter assay, qRT-PCR, and western blot were used to verify the regulatory relationship between METTL14 and CCNL2. RIP experiments verified the regulatory relationship between YTH domain-containing family protein (YTHDF2) and CCNL2. Cell viability was detected by MTT method, and cell invasion ability was detected by Transwell.Results:Compared with normal cells (0.24±0.02) and tissues (0.18±0.02) , BC cells MCF-10A (0.47±0.03, t=11.05, P<0.001) and HS-578T (0.41±0.03, t=8.17, P=0.001) and BC tissues (0.39±0.02, t=12.86, P<0.001) m6A level increased. Compared with normal tissues (1.00±0.26) (0.84±0.07) , METTL14 mRNA (1.57±0.28, t=13.50, P<0.001) and protein levels (1.66±0.11, t=10.89, P<0.001) in BC tissues were significantly increased high. Compared with the control group (100.00±10.11) (1.00±0.12) , the BC cell invasion ability (54.15±6.21, t=6.69, P=0.003) and activity (0.64±0.06, t=4.65, P=0.010) were weakened. Compared with the control group (100±11.05) (1±0.13) , the BC cell invasion ability (175.31±13.45, t=7.49, P=0.002) and activity (2.16±0.16, t=9.75, P=0.002) in the METTL14 overexpression group were enhanced, and the effects of METTL14 on cell invasion (137.41±12.64, t=3.56, P=0.024) and activity (1.64±0.15, t=5.59, P=0.005) were partially reversed after m6A inhibitor treatment change. Compared with normal tissues, CCNL2 expression was down-regulated in BC tissues, and the interaction between CCNL2 and METTL14 was confirmed. Compared with the control group (1.00±0.1) (0.64±0.05) , knockdown of METTL14 could make CCNL2 mRNA (1.67±0.05) . 0.13, t=7.08, P=0.002) and protein (1.09±0.09, t=7.57, P=0.002) were up-regulated. METTL14 knockout enhanced the stability of CCNL2 mRNA through a YTHDF2-dependent pathway, compared with sh-METTL14 group (50.47±5.16) (0.52±0.05) , BC cell invasion ability of sh-METTL14+sh-CCNL2 group (71.69±6.41, t=4.47, P=0.011) and activity (0.64±0.05, t=2.94, P=0.042) were improved. Conclusion:METTL14 inhibits the expression of CCNL2 through m6A modification to enhance the invasion and activity of BC cells.

Effects of deep learning- versus atlas-based automatic contouring methods on the contouring of organs-at-risk in rectal cancer / 中国基层医药

Objective:To investigate the effects of deep learning-based AiContour ??versus atlas-based Raystation ?? automatic contouring methods on the contouring of organs-at-risk on CT images of patients with rectal cancer who undergo radiotherapy, providing evidence for clinical application. Methods:Fifty patients with rectal cancer who received treatment during January to June 2020 in Zhejiang Provincial People's Hospital (Affiliated Hospital of Hangzhou Medical College) were included in this study. The CT images from 20 patients with rectal cancer that had been contoured by experienced radiotherapist were selected as target images and automatically contoured using the data template library of AiContour ?? and Raystation ?? automatic contouring methods. Hausdorff distance, mean distance to agreement, dice similarity coefficient, Jaccard coefficient were used to quantitatively evaluate the accuracy of the volume of contour of organs-at-risk automatically sketched by the two methods. Results:There was no significant difference in Hausdorff distance in left femoral head [(6.81 ± 2.66) vs. (7.24 ± 2.10)], right femoral head [(7.38 ± 3.91) vs. (8.14 ± 3.71)], pelvis [(24.00 ± 9.01) vs. (24.66 ± 9.67)] between AiContour ?? and Raystation ?? automatic contouring methods ( tleft femoral head = -0.831, tright femoral head = -0.821, tpelvis = -0.357, all P > 0.05). Significant differences were observed in mean distance to agreement, dice similarity coefficient and Jaccard coefficient of organs-at-risk (all P < 0.05). The mean values of dice similarity coefficient automatically sketched by AiContour ?? method were > 0.7. The DSC of left kidney, right kidney, rectum and bladder automatically sketched by Raystation ?? method were < 0.7, and the dice similarity coefficient values of other organs-at-risk automatically sketched by Raystation ?? method were > 0.7. In addition, Hausdorff distance, mean distance to agreement and Jaccard coefficient values of organs-at-risk automatically sketched by AiContour ?? method were superior to those automatically sketched by Raystation ??. Conclusion:After slight modification, the organs-at-risk automatically sketched by AiContour ?? and Raystation ?? methods can meet clinical requirement. The contouring effects provided byAiContour ?? method were superior to those provided by Raystation ?? method.

Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 patients

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. MethodBetween January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection rates, the prevalence and abundance of microbial communities in these COVID-19 patients were determined. FindingsNotably, respiratory microbial co-infections were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death one month after ICU admission. InterpretationOur findings identified distinct patterns of co-infections with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. FundingNational Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Author summaryIn this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.

A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution

Fighting the COVID-19 epidemic summons deep understanding of the way SARS-CoV-2 taps into its host cell metabolic resources. We describe here the singular metabolic background that creates a bottleneck constraining coronaviruses to evolve towards likely attenuation in the long term. Cytidine triphosphate (CTP) is at the crossroad of the biosynthetic processes that allow the virus to multiply. This is because CTP is in demand for three essential steps. It is a building block of the virus genome, it is required for synthesis of the cytosine-based liponucleotide precursors of the viral envelope and, finally, it is a critical building block of the host transfer RNAs synthesis. The CCA 3-end of all the transfer RNAs required to translate the RNA genome and further transcripts into the proteins used to build active virus copies is not coded in the human genome. It must be synthesized de novo from CTP and ATP. Furthermore, intermediary metabolism is built on compulsory steps of synthesis and salvage of cytosine-based metabolites via uridine triphosphate (UTP) that keep limiting CTP availability. As a consequence, accidental replication errors tend to replace cytosine by uracil in the genome, unless recombination events allow the sequence to return to its ancestral sequences. We document some of the consequences of this situation in the function of viral proteins. We also highlight and provide a raison detre to viperin, an enzyme of innate antiviral immunity, which synthesizes 3-deoxy-3',4-didehydro-CTP (ddhCTP) as an extremely efficient antiviral nucleotide.

Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

Multiple approaches for massively parallel sequencing of HCoV-19 genomes directly from clinical samples

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

Effect of large-scale testing platform in prevention and control of the COVID-19 pandemic: an empirical study with a novel numerical model

BackgroundChina adopted an unprecedented province-scale quarantine since January 23rd 2020, after the novel coronavirus (COVID-19) broke out in Wuhan in December 2019. Responding to the challenge of limited testing capacity, large-scale standardized and fully-automated laboratory (Huo-Yan) was built as an ad-hoc measure. There was so far no empirical data or mathematical model to reveal the impact of the testing capacity improvement since the quarantine. MethodsWe integrated public data released by the Health Commission of Hubei Province and Huo-Yan Laboratory testing data into a novel differential model with non-linear transfer coefficients and competitive compartments, to evaluate the trends of suspected cases under different nucleic acid testing capacities. ResultsWithout the establishment of Huo-Yan, the suspected cases would increased by 47% to 33,700, the corresponding cost of the quarantine would be doubled, and the turning point of the increment of suspected cases and the achievement of "daily settlement" (all daily new discovered suspected cases were diagnosed according to the nucleic acid testing results) would be delayed for a whole week and 11 days. If the Huo-Yan Laboratory ran at its full capacity, the number of suspected cases would decrease at least a week earlier, the peak of suspected cases would be reduced by at least 44% and the quarantine cost could be reduced by more than 72%. Ideally, if a daily testing capacity of 10,500 could achieved immediately after the Hubei lockdown, "daily settlement" for all suspected cases would be achieved immediately. ConclusionsLarge-scale and standardized clinical testing platform with nucleic acid testing, high-throughput sequencing and immunoprotein assessment capabilities need to be implemented simultaneously in order to maximize the effect of quarantine and minimize the duration and cost. Such infrastructure like Huo-Yan, is of great significance for the early prevention and control of infectious diseases for both common times and emergencies.

Implementation of radiotherapy in a tertiary hospital in Zhejiang province during the epidemic of COVID-19 / 中华放射医学与防护杂志

Objective:To explore the clinical practice of delivering radiotherapy during the outbreak of 2019 novel coronavirus disease(COVID-19).Methods:During this epidemic period, available method including but not limited to: strict disinfection, body temperature monitoring and staff training of relevant knowledge, were used to ensure the safety of radiotherapy treatment. Statistical analysis was performed to study the relevant data including proportion of patients receiving radiotherapy for different purposes, time from scanning to the first time of radiation delivery and degree of satisfaction in the view of staffs and patients, respectively.Results:A total of 60 patients received radiation therapy in the department of radiotherapy of Zhejiang Provincial People′s Hospital (2020-02-11). Compared with the same period in 2019 (after the Spring Festival), the total number of patients receiving radiotherapy was decreased from 72 to 60(83.3%). Among them, the number of patients receiving palliative radiation therapy decreased significantly, while the proportion of radical, preoperative and/or postoperative radiotherapy/radiochemotherapy did not significantly decrease. There was significant difference between two years ( χ2=6.967, P<0.05). The median time for newly admitted patients to receive radiotherapy was two days, which was not significantly longer than the interval in 2019 ( P>0.05). Staff and patients were generally satisfied with the current prevention measures. Conclusions:Using a variety of prevention and control method, and taking full account of medical safety and patient benefits, radiation-related activities can be carried out during the epidemic.

Implementation of radiotherapy in a tertiary hospital in Zhejiang province during the epidemic of COVID-19 / 中华放射医学与防护杂志

Objective@#To explore the clinical practice of delivering radiotherapy during the outbreak of 2019 novel coronavirus disease(COVID-19).@*Methods@#During this epidemic period, available methods including but not limited to: strict disinfection, body temperature monitoring, learning relevant knowledge by all staffs to ensure the safety of radiotherapy treatment. Relevant data including proportion of radiotherapy, time from scanning to the first time of radiation delivery and degree of satisfaction in the view of staffs and patients, respectively.@*Results@#A total of 60 patients received radiation therapy in the department of radiotherapy of Zhejiang Provincial People’s Hospital (2020-02-11). Compared with the same period in 2019 (after the Spring Festival), the total number of patients receiving radiotherapy was decreased from 72 to 60(83.3%). Among them, the number of patients receiving palliative radiation therapy decreased significantly, while the proportion of radical, preoperative and/or postoperative radiotherapy/radiochemotherapy did not significantly decrease. There was significant difference between different years (χ2=6.967, P<0.05). The median time for newly admitted patients to receive radiotherapy was two days, which was not significantly longer than the interval in 2019 (P>0.05). Staffs and patients were generally satisfied with the current prevention measures.@*Conclusions@#Using a variety of prevention and control methods, and taking full account of medical safety and patient benefits, radiation-related activities can be carried out during the epidemic.

A case of severe fever with thrombocytopenia syndrome virus related encephalitis / 中华神经科杂志

The severe fever with thrombocytopenia syndrome virus (SFTSV),a new RNA virus,was discovered in recent years,which can lead to fever,thrombocytopenia and multiple organ dysfunction.Picks is the main media A case of a SFTSV-related encephalitis diagnosed by second-generation gene sequencing was reported here.The patient had fever,disturbance of consciousness,convulsions,with thrombocytopenia and enzymatic indicators increased significantly.After active anti-virus and supportive treatment,the prognosis was good.It is our aim to suggest that,in the epidemic season,when you meet thesimilar patients like this,you should consider the possibility of SFTSV-related encephalitis.Virus nucleic acid detection and second-generation gene sequencing technology are helpful for timely diagnosis and treatment and reducing mortality of the disease.

Application of EPID-based 3D dose reconstruction in cancer patients / 中华放射肿瘤学杂志

Objective To perform 3D dose reconstruction based on electronic portal imaging device ( EPID) of linear accelerator for the static intensity-modulated using Edose, a dose verification system, Aiming to assist the radiotherapy professionals to better understand the radiotherapy organs at risk and target dose changes. Methods CBCT image was acquired for patients with head and neck cancer and thoracic cancer once a week for a total of six times. Subsequently,CBCT images and planning CT images were subject to rigid registration and exported to the Edose software. According to the setup error, EPID-based three-dimensional dose reconstruction was performed by using Edose software. The gamma passing rate and dose of different organs at risk ( OARs ) were analyzed and statistically compared. Results For patients with nasopharyngeal carcinoma,the intra-fractional Dmax of the spinal cord was more significantly fluctuated and higher compared with the planning dose, whereas the intra-fractional Dmax of the brainstem did not significantly fluctuate. The V30 of the parotid gland significantly changed with a maximum increase of 28. 69％ per fraction. For patients with thoracic tumors,the Dmax of the spinal cord was slightly changed,and the actual doses in the lung and heart were higher than the planning doses. The average deviation of the pulmonary V5 was up to 16. 99％ between the actual and planning doses with statistical significance ( P<0. 05).According to the analysis of gamma passing rate,significant dose changes occurring in the OARs were detected in the 16th fraction for the head and neck cancer and the 24th fraction for the thoracic neoplasms. Conclusions The dose changes in the OARs can be obtained by reconstructing the EPID-based 3D dose distribution using the Edose software for each fraction, which can better protect the OAR, enhance the coverage of target dose and provide certain reference for dose-guided and self-adaptive radiotherapy.

Comparison of clinical prognosis between stereotactic body radiotherapy and surgical treatment for early-stage non-small cell lung cancer after propensity score matching / 中华放射肿瘤学杂志

Objective To evaluate the clinical efficacy between stereotactic body radiotherapy (SBRT) and surgical treatment for stage Ⅰ-Ⅱ non-small cell lung cancer (NSCLC).Methods Clinical data of 120 patients with early-stage NSCLC who underwent SBRT or surgical treatment in Zhejiang Cancer Hospital from 2012 to 2015 were retrospectively analyzed.Propensity score matching was carried out between two groups.Sixty eligible patients were enrolled in each group.In the SBRT group,the 80％ isodose line covered 95％ of the planning target volume,and the 100％ isodose line covered 100％ of the internal gross tumor volume.The fractional dose was 5-15 Gy and the median biologically equivalent dose was 100 Gy (range:57.6-150.0 Gy).In the operation group,32 patients underwent video-assisted thoracoscopic lobectomy and 9 patients underwent wedge resection or segmentectomy.Results All patients successfully completed corresponding treatment and were followed up.The median follow-up was 32.3 months (range:8.6-68.4 months).In the operation group,3 patients died from infection within postoperative 90 d,whereas no case died in the SBRT group (P=0.079).In the SBRT group,3 patients died of other factors besides tumor (cerebral infarction,heart disease,etc.) during follow-up.Local-regional recurrence occurred in 12 patients including 5 cases in the operation group and 7 in the SBRT group (P=0.543).In the operation group,11 patients experienced distant metastases with a median disease-free survival (DFS) of 33.5 months.In the SBRT group,6 patients had distant metastases and the median DFS was 38.4 months (P=0.835,P=0.178).In the SBRT group,the 1-and 3-year overall survival rates were 93％ and 83％,and 95％ and 83％ in the operation group (P=0.993).Conclusions The 1-and 3-year overall survival rates and local control rate do not significantly differ between SBRT and operation for patients with early-stage NSCLC.

Impacts of patient factors on intensity-modulated radiotherapy planning after breast-conserving surgery for breast cancer / 中华放射肿瘤学杂志

Objective To investigate the impacts of planning target volume (VPTV),maximal heart distance (MHD),central lung distance (CLD),and cardiothoracic ratio (CTR) on intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer.Methods Forty-eight patients with breast cancer (31 with left-sided breast cancer and 17 with right-sided breast cancer) who received whole-breast IMRT after breast-conserving surgery in our hospital from 2016 to 2017 were enrolled as subjects.The prescribed radiation dose tor PTV was 50 Gy in 25 fractions.In IMRT planning for each patient,the objective function was optimized using physical parameters and the equivalent uniform dose.The relationship of influencing factors with dose-volume histogram,conformal index (CI),and homogeneity index (HI) for organ at risk was predicted using univariate and multivariate linear regression analyses.Results CTR and VPTV were independent influencing factors for CI in patients with left-sided breast cancer (R2=0.56,P=0.04;R2 =0.56,P=0.00).CLD was an independent influencing factor for HI in patients with left-sided breast cancer (R2=0.17,P=0.023).VPTV was an independent influencing factor for CI in patients with right-sided breast cancer (R2 =0.48,P=0.00).MHD and CTR were predictors for VHeart30 of the heart.MHD and CLD were predictors for DmaxHeart of the heart.The prediction formulae for left-sided breast cancer were CI=0.38+0.32CTR and HI=1.06+0.02CLD.CI was 0.48 at the right side.At the left side,Vlung20=12.68+3.18CLD,Vlung10=18.78+4.3CLD,Vlung5=26.2+5.2CLD,and Dmeanlung=686.7+210.ICLD.For the heart,VHeart30=-13.65+30.5CTR+1.9MHD and DmaxHeart =5 140.1 +248.9MHD-195.6CLD.There was no correlation of patient's heart volume with MHD,VHeart10,VHeart5,DmeanHeart,or DmaxHeart.There was no correlation of whole lung volume with CLD,Vlung20,Vlung10,Vlung5,or Dmeanlung.The mean values of CI and HI were 0.63± 0.06 (0.46-0.72) and 1.09± 0.02 (1.07-1.14-) in radiotherapy plans for left-sided breast cancer,and 0.65± 0.08 (0.4-8-0.76) and 1.09± 0.04 (1.03-1.18) in radiotherapy plans for right-sided breast cancer,respectively.Conclusions CTR,CLD,and MHD can predict the rationality of each parameter in IMRT planning for left-sided breast cancer rather than right-sided breast cancer.The obtained formulae can help physicians choose the optimal setting mode for radiation field and improve the quality of treatment plans.

Outcome and long-term efficacy of four facio-cervical fields conformal radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To evaluate the outcomes of 255 patients with nasopharyngeal carcinoma (NPC) treated with four facio-cervical fields conformal radiotherapy (4F-CRT). RESULTS: In one patient's 3 different RT treatment modalities, the 4F-CRT techniques resulted in sharper of the dose-volume histograms (DVHs) for primary gross tumor volume (PGTVnx) and planning target volume (PTVnx), similar to the intensity modulated radiation therapy (IMRT). The median follow-up duration was 43 months. Locoregional relapse and distant metastases as the first treatment failure events occurred in 32 (32/255, 12.5%) and 20 (30/255, 11.8%) patients, respectively. The 3-year and 5-year local control, disease-free survival, and overall survival rates were 83.3%, 82%, 83.8%, and 76.1%, 73.2%, 76.3% respectively. Univariate analysis displayed that clinical stage, T-stage, N-stage, and tumor response were related to prognosis. Multivariate analysis indicated that age, T-stage, N-stage, and combined chemotherapy were independent prognosticators. The incidence of grade 1-2 acute mucositis and leukocytopenia were 93.7% and 91.0%, respectively, with no cases of grade 4 toxicity detected. MATERIALS AND METHODS: From November 2007 to December 2011, 255 patients with histologically diagnosed, non-metastatic NPC were enrolled into this study and received 4F-CRT. Magnetic resonance imaging scans of the nasopharynx were performed on every patient. All patients received definitive radiotherapy with 6 MV X-rays using conventional fractions at 2 Gy daily, 5 fractions per week, and 231 patients with stage IIb-IV received concurrent chemotherapy and cisplatin-based adjuvant chemotherapy. The accumulated survival was calculated according to the Kaplan-Meier method; the log-rank test was used to compare survival differences. Multivariate analysis was performed using Cox's proportional hazard model. CONCLUSIONS: Compared with the conventional treatment plans, the 4F-CRT plan delivered more dose to cover the tumor volume and reduces the doses of the normal tissues including the parotid gland, TMJs and so on. The long-term efficacy of 4F-CRT is satisfactory and its toxicities are tolerable.

Experience and efficacy of SBRT for lung cancer:an analysis of 200 patients / 中华放射肿瘤学杂志

Objective To evaluate the safety and clinical efficacy of stereotactic body radiation therapy (SBRT) for lung cancer.Methods A retrospective analysis was performed on 200 patients with primary non-small cell lung cancer (NSCLC)(118 patients) or solitary pulmonary metastasis (82 patients) who underwent SBRT in Zhejiang Cancer Hospital from January 2012 to September 2015.The 80% isodose line covered 95% of the planning target volume,and the 100% isodose line covered 100% of the internal gross tumor volume.The fractional dose was 4.0-18.0 Gy daily or every other day,and the biologically equivalent dose ranged from 40.0 to 151.2 Gy (median 100 Gy).Results All patients completed treatment.The follow-up rate was 96.0%.The complete response and partial response rates were 14.8%(17/115) and 65.2%(75/115) for the primary tumor group,versus 25%(19/77) and 38%(29/77) for the metastasis group.The incidence rates of grade Ⅱ and Ⅲ acute radiation pneumonitis were 4.7% and 3.1%,respectively.The median follow-up was 14.9 months.The 1-and 2-year local control rates were 95.7% and 84.3% for the primary tumor group,versus 92% and 73% for the metastasis group.The 1-and 2-year overall survival rates were 94.5% and 92.0% for the primary tumor group,versus 85% and 62% for the metastasis group.Conclusions SBRT is a safe and effective treatment for early primary NSCLC and solitary pulmonary metastasis,resulting in high 1-and 2-year local control and overall survival rates and low rate of complications.

Study of oxaliplatin combined with capecitabine in the preoperative gemcitabine concurrent chemotherapy for improving the local control rate of colorectal cancer and anal sphincter preservation rate / 中国基层医药

Objective To investigate the effect of oxaliplatin combined with capecitabine on the rate of local control and anal sphincter preservation of rectal cancer.Methods Eighty patients with stage Ⅱ/Ⅲ colorectal adenocarcinoma were randomly divided into control group and observation group,each group in 40cases.The patients in the observation group were treated with oxaliplatin and capecitabine.The control group was treated with oxaliplatin combined with leucovorin and 5-fluorouracil.The patients were followed up for 2~4 weeks.The local curative effect, perioperative biochemical index,R0 (excision margin without cancer cell) resection rate and sphincter preserving rate were compared between the two groups.Results In the control group, the short-term curative effect was 47.50%, which in the observation group was 60.00%, the difference was statistically significant (x2=4.22,P0.05).The R0 resection rates of the control group and the observation group were 62.50%,57.50% (x2=0.67,P>0.05).The anal sphincter preservation rates of the control group and observation group were 32.50%,37.50% respectively (x2=0.67,P>0.05).The local control rates of the control group and observation group were 90.00%,92.50%,which of the observation group was higher than the control group, but the difference was not statistically significant(x2 =0.32,P>0.05).Conclusion The combination of oxaliplatin and capecitabine can improve the local curative effect in patients with rectal cancer without affecting the biochemical indicators of perioperative patients, but the effect of R0 resection rate and preserving anus rate in patients with rectal cancer compared with the chemotherapy regimen of FOLFOX4 has no significant difference, it is worthy of clinical promotion.

Expression of cerebral Kuppel-like factor 2 in focal cerebral ischemia-reperfusion injury in rats and intervention effect of nuclear factor kappa B inhibitor / 中国脑血管病杂志

Objective To investigate the expression of Kuppel-like factor 2( KLF2 )after focal cerebral ischemia-reperfusion( I/R)injury in rats and the intervention effect of nuclear factor kappa B ( NF-κB)inhibitor. Methods Sixty healthy male SD rats were randomly divided into a sham operation group,an I/R group,and a NF-κB inhibitor group( n=20 in each group). A focal cerebral I/R model was induced by the intraluminal suture method,and NF-κB inhibitor( pyrrolidinedithio carbamate,PDTC)was given to intervene. The observation time points were 6,12,24,and 48 hours after I/R. Reverse transcription-polymerase chain reaction(PCR)and Western blot were used to measure KLF2 mRNA and protein expression in ischemic brain tissue. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum tumor necrosis factorα( TNF-α),and they were compared among groups. Results Compared with the sham operation group,the expression levels of KLF2 mRNA and protein in I/R group in the ischemic brain tissue at each time point were averagely decreased( the relative expression levels of KLF2 mRNA:0. 46 ± 0. 03 vs. 0. 82 ± 0. 04,0. 30 ± 0. 04 vs. 0. 78 ± 0. 05,0. 18 ± 0. 04 vs. 0. 76 ± 0. 02,0. 26 ± 0. 02 vs. 0. 81 ± 0. 04,respectively;the relative expression levels of KLF2 protein:0. 46 ± 0. 04 vs. 0. 80 ± 0. 02,0. 30 ± 0. 02 vs. 0. 79 ± 0. 02,0. 15 ± 0. 02 vs. 0. 77 ± 0. 01,0. 24 ± 0. 01 vs. 0. 79 ± 0. 02,respectively). They reached the lowest values at 24 hours after I/R,while the serum TNF-αlevels were increased. There were significant differences(all P<0. 05). After giving NF-κB inhibitor PDTC,the expression levels of KLF2 mRNA and protein at 6,12,24,and 48 hours after I/R were upregulated differently compared with the I/R group. The relative expression levels of KLF2 mRNA were 0. 61 ± 0. 04,0. 44 ± 0. 03,0. 34 ± 0. 02,and 0. 43 ± 0. 04, respectively. Those of KLF2 protein were 0. 60 ± 0. 02,0. 43 ± 0. 02,0. 33 ± 0. 01,and 0. 44 ± 0. 03, respectively,while the levels of TNF-αwere decreased. There were significant differences(all P<0. 05). There was a negative correlation between the KLF2 mRNA levels and the serum TNF-αlevels at each time point in the I/R group and the PDTC group( r= —0. 728 ,P<0. 05 ). Conclusions The expression levels of KLF2 mRNA in brain tissue are decreased after I/R,and it is negatively correlated with the serum TNF-α levels. It may be involved in the pathological process of I/R by NF-κB pathway mediated inflammatory reaction.

Development of Droplet Digital Polymerase Chain Reaction for Quantifying Escherichia Coli O157:H7 / 分析化学

A droplet digital polymerase chain reaction ( ddPCR) method for quantifying E. coli O157:H7 by targeting rfbE gene was developed. The probe concentration in ddPCR was optimized and the linearity range, precision, limit of detection ( LOD) and limit of quantification ( LOQ) were also evaluated. The optimized probe concentration was 300 nmol/L. The ddPCR response was linear over the E. coli O157:H7 genome DNA concentration range from 4 to 1. 25×105 copies in 20 μL ddPCR system and the linear correlation coefficient (R2) was 0. 999. The ddPCR precision (RSD) was less than 5% over the DNA concentration range from 760 to 88400 copies/20 μL. The LOD and LOQ was 3 copies in 20 μL and 4 copies in 20 μL, respectively. Specificity test showed that the ddPCR was specific for detecting E. coli O157:H7. Both ddPCR and standard real time quantitative PCR showed the same results for 16 real samples of chicken meat, pork and beef, which indicated that ddPCR method was suitable for detection of E. coli O157:H7 in food.