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Objective@#To investigate the associations between early life exposure to particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ) and the risk of autism spectrum disorder (ASD) among school aged children.@*Methods@#A total of 165 children with ASD and 165 age and gender matched typical development (TD) children were recruited. Children s basic information were obtained via questionnaires, and the severity of ASD symptoms was assessed with Social Responsiveness Scale (SRS). Early life PM 2.5 exposure (preconception, entire pregnancy, and the first two years after birth) were extracted from the Tracking Air Pollution in China (TAP) datasets. Conditional Logistic regression and generalized linear model were used to evaluate the associations of early life exposure to PM 2.5 with the risk and the ASD severity symptoms, respectively.@*Results@#The PM 2.5 exposure of ASD group during preconception[(55.08±9.34)μg/m 3], entire pregnancy[(50.44±8.71)μg/m 3], the first year after birth [(45.04± 8.25 )μg/m 3] and the second year after birth [(40.19±7.12)μg/m 3] were significant higher than those in TD children [(47.66± 7.63 , 44.19±7.16, 38.95±6.07, 35.76±5.65)μg/m 3]( t =7.94, 7.13, 7.70, 6.32, P <0.05). After adjusting for potential confounding, each increase of 1 μg/m 3 in PM 2.5 was associated with higher risk of ASD during preconception ( OR=1.21, 95%CI =1.13-1.29), entire pregnancy( OR=1.18, 95%CI =1.11-1.26), the first year after birth ( OR=1.30, 95%CI =1.18-1.43) and the second year after birth ( OR=1.29, 95%CI =1.17-1.42). No similar results were observed regarding the analyses of SRS total and sub scale scores( P >0.05).@*Conclusion@#Early life exposure to PM 2.5 is relate to the risk of ASD, these findings indicated that more attention should be paid to ambient PM pollution in the early life prevention and control of ASD.
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Objective@#To investigate the association between parenting style and sleep problems among school aged children with autism spectrum disorder (ASD).@*Methods@#A total of 98 children with ASD aged 6-10 years old and 98 age and gender matched typically developing (TD) children from mainstream schools were recruited. Parenting style and sleep problems were measured via Parent Behavior Inventory (PBI) and Children s Sleep Habits Questionnaire(CSHQ), respectively. The symptom severity and intelligence level were also evaluated. Generalized linear model was used to analyze the relationship between parenting style and sleep problems.@*Results@#There was no statistically significant difference in the parenting style of the two groups of children( P > 0.05 ); weekend sleep time of children with ASD was significantly shorter than that of the TD group [(9.1±0.7)(9.5±0.8)h, P < 0.01 ], and the score of sleep onset delay was significantly higher than that of the TD group[(1.8±0.7)(1.5±0.7), P <0.01]. However, there was no statistically significant difference in the incidence of total sleep problems and various problems between the two groups of children( P >0.05). The parental support/engagement of children with ASD was negatively associated with the total score of sleep problems( β=-2.68, 95%CI =-4.88--0.47), bedtime resistance ( β=-1.65, 95%CI =-2.54--0.77) and sleep anxiety( β=-1.01, 95%CI =-1.70--0.32). The parental hostility/coercion was positively correlated with score of daytime sleepiness( β=1.41, 95%CI =0.53-2.29)( P <0.05).@*Conclusion@#Parenting style of support/engagement is associated with lower sleep problems in children with ASD, while hostile/coercion is associated with higher sleep problems. It should be improve parental style to reduce the sleep problems in children with ASD.
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Objective@#To explore changes in the social interactions of school aged children with autism spectrum disorder (ASD) enrolled in ordinary schools and special education institutions during a one year observation period.@*Methods@#A total of 44 children with ASD were recruited from the Research Center of Children and Adolescent Psychological and Behavioral Development in the Department of Public Health, Sun Yat sen University, during 2017 and 2018. At the baseline and follow up periods, a self report questionnaire (completed by parents) was administered in order to collect demographic information related to the children, the survey included the Social Responsiveness Scale (SRS), Strengths and Difficulties Questionnaire (SDQ), Social Communication Questionnaire (SCQ), Screen for Child Anxiety Related Emotional Disorder (SCARED) and the Swan son Nolan and Pelham, Version IV Scale(SNAP-IV).@*Results@#At baseline, compared with children in ordinary schools, the total score of SRS (114.56±6.02, 93.63 ±3.82) and its subscale scores (social awareness:13.54±0.71, 11.02±0.45; social cognition:22.73±1.16, 18.19±0.73; social interaction:37.47±2.12, 30.40±1.35; autistic mannerisms: 23.11±1.70, 19.02±1.08) were higher in children attending special education institutions, as well as the SCQ total score (20.37±1.60, 12.92±1.02) and its subscale scores(social interaction domain:8.77±0.92, 4.23±0.58; social communication domain:6.07±0.55, 4.19±0.35)( P <0.05). Further comparison of baseline and follow up results showed no significant difference in time effect or in the interaction between time and the educational environment( P >0.05).@*Conclusion@#Compared with special education institutions, school aged children with ASD in ordinary schools had lower levels of social impairment. During the one year observation period, there was no correlation between the educational environment and changes in symptoms of children and their parents. Parents should choose an appropriate educational environment according to the children s abilities, and ordinary schools and teachers should be prepared for inclusive education.
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Objective@#To study the relationship between motor coordination, social communication impairment, and restricted/repetitive behaviors (RRBs) in children with autism spectrum disorder (ASD).@*Methods@#A total of 123 ASD children aged 2-12 were recruited from rehabilitation service institutions for autistic children in Guangzhou, including 105 boys and 18 girls. The Developmental Coordination Disorder Questionnaire, Social Communication Questionnaire, and Restrictive Behavior Scale Revised were collected to measure motor coordination, social communication skills and RRBs, respectively. Multiple linear regression was used to explore the association between motor coordination and core symptoms.@*Results@#In children aged 2-5 years old, those without motor coordination deficits scored lower in social interaction (7.73±4.00) than others (9.76±2.90)( Z=-2.29, P <0.05). In children aged 6-12 years old, those without motor coordination deficits scored lower in restricted, repetitive, and stereotyped patterns of behavior (4.22±1.93), repetitive sensory-motor behaviors (3.91±2.63), and insistence on sameness (13.52±10.59) than those with motor coordination deficits (6.11±1.54, 14.00±8.49, 31.33±15.05)( Z=-2.48, -3.83, -3.28, P <0.01)。Multiple linear regression analysis showed that fine motor/handwriting and control during movement were negatively correlated with the severity of social communication impairment and RRBs respectively among children aged 2-5 and 6-12( β=-0.85--0.03, -2.98--0.17, P <0.05).@*Conclusion@#Among autistic children, those with motor deficits suffered from more severe core symptoms. Motor assessment should be included in the ASD screening, diagnosis and management. Motor intervention should also be promoted in the rehabilitation in order to improve the prognosis and life quality.
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Abstract@#In recent years, the incidence of mental disorders among children and adolescents has been increasing worldwide. To decrease the incidence of mental health problems, many relevant policies and regulations have been successively issued and mental health services have been implemented in China. The article focused on the development and progression of mental health problems during the transition from childhood to adolescence, emphasized possible determinants on the association between physical and mental health, and presented causality in psychiatry and related models. Especially, the article highlighted some viewpoints from the clinical perspective and put forward relevant considerations and suggestions.
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Objective:To evaluate the role of adenosine monophosphate-dependent protein kinase/p38 mitogen-activated protein kinase/nuclear factor E2-associated factor 2 (AMPK/p38 MAPK/Nrf2) pathway in myocardial ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Clean-grade healthy Sprague-Dawley male rats, aged 2-3 months, weighing 220-280 g, were fed with a high fat diet, and 1% streptozotocin 50 mg/kg was intraperitoneally injected for 4 consecutive days to develop the model of diabetes mellitus.Thirty diabetic rats were divided into 3 groups ( n=10 each) using the random number table method: sham operation group (sham group), myocardial I/R group (I/R group), and AMPK inhibitor compound C+ myocardial I/R group (C+ I/R group). The model of myocardial I/R injury was developed by ligation of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion.Compound C 0.5 mg/kg was injected via the caudal vein at 30 min before ischemia in C+ I/R group, while the equal volume of normal saline was given instead in Sham group and I/R group.At 120 min of reperfusion, the percentage of myocardial infarct size was calculated, the serum concentrations of creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay, the levels of glutathione (GSH), superoxide dismutase (SOD) and reactive oxygen species (ROS) in myocardial tissues were measured by enzyme-linked immunosorbent assay, and the expression of AMPK, phosphorylated AMPK (p-AMPK), phosphorylated p38 MAPK (p-p38 MAPK), Nrf2 and heme oxygenase-1 (HO-1) in myocardium was determined by Western blot. Results:Compared with Sham group, the percentage of myocardial infarct size and serum CK-MB and LDH levels were significantly increased, the levels of GSH and SOD in myocardial tissues were decreased, ROS level was increased, and the expression of AMPK, p-AMPK, p-p38 MAPK, Nrf2 and HO-1 was up-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct size and serum CK-MB and LDH levels were significantly increased, the levels of GSH and SOD in myocardial tissues were decreased, ROS level was increased, and the expression of AMPK, Nrf2 and HO-1 was down-regulated in C+ I/R group ( P<0.05). Conclusions:AMPK/p38 MAPK/Nrf2 signaling pathway is involved in the mechanism of endogenous antioxidant stress during myocardial I/R in diabetic rats.
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In recent years, with the development of rectal cancer treatment mode, the anal preservation rate in rectal cancer patients has been gradually increased. In addition to preserving the anal shape, the preservation of anal function is also gradually valued. In this article, literature review on anal function related to radiotherapy and chemotherapy for rectal cancer patients was conducted, aiming to elaborate the evaluation criteria and research status of anal function in rectal cancer patients.
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Primary hepatocellular carcinoma is the fourth most common malignant tumor in China, with the 2nd highest mortality rate. Clinical prognosis of hepatocellular carcinoma complicated with portal vein tumor thrombus is extremely poor. At present, multiple interventions have been adopted to treat primary hepatocellular carcinoma complicated with portal vein tumor thrombus, such as surgery, radiotherapy and targeted therapy, etc. In this article, the treatment of primary hepatocellular carcinoma with portal vein tumor thrombus was summarized, and the effect and prospect of radiotherapy based comprehensive treatment were illustrated.
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Objective:To evaluate the compliance with Chinese Residency Training Program of radiation oncology and provide reference for the improvement of system reform and base construction.Methods:An survey was conducted among residents who had completed residency training program of radiation oncology by online questionnaires in four dimensions, including the fulfillment of training center in hardware, personnel and procedures, the compliance with syllabuses, mechanism of trainee evaluation, and the passing rate and satisfaction degree of trainees.Results:The results showed that most training centers fulfilled the requirement of equipment, mentoring personnel and procedures. The training syllabuses had been followed and integrated with organization multi-modalities. The trainees with high degree of satisfaction accounted for 65.6%, and the final qualification passing rate reached 75.5%. However, there were less reference textbooks, insufficient training in general medicine, limited clinical practice, and low output in academic publication.Conclusions:The residency training program of radiation oncology has been established in China and achieved notable progress. For the further improvement, quantitative optimization of procedures, increasing opportunity of practice and strengthening scientific research involvement would be beneficial.
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Objective:To detect the mRNA expression and methylation status of leucine rich repeat containing 55(LRRC55) gene in pancreatic carcinoma tissues, and discuss the clinical value.Methods:Resected pancreatic ductal adenocarcinoma and normal adjacent specimens from 37 patients admitted in General Surgery of First Affiliated Hospital of Naval Medical University were collected from May 2019 to May 2021. Another two normal pancreas specimens and two blood samples from healthy adults were also collected. All patients′ age, gender, tumor location, tumor size, tumor differentiation, TNM staging, lymphatic metastasis, CEA and CA19-9 level were recorded. Bisulfite treatment of genomic DNA and sequencing analysis was used to study methylation patterns in CpG islands of the promoter for LRRC55 gene in fresh tissues from 2 pancreatic adenocarcinoma and adjacent tissues, 2 normal pancreatic tissues, 2 pancreatic cancer cell lines (PaTu8988 and ASPC1). LRRC55 mRNA in 35 pancreatic adenocarcinoma and adjacent tissues was detected by real-time quantitative PCR and the correlations with clinical parameters were analyzed.Results:CpG islands of LRRC55 in pancreatic adenocarcinoma tissues and pancreatic cancer cell lines was highly methylated and the mean methylation rate was 53% and 71%, respectively; while LRRC55 gene in pancreatic adjacent tissues and normal pancreatic tissues was lowly methylated, and the mean methylation rate was 8% and 11%. The relative expression in the pancreatic adenocarcinoma tissues and the paired adjacent normal tissues was 0.21 (0.02, 1.00 ) and 0.98 (0.33, 3.66 ), respectively; the former was significantly lower than the later and the difference was statistically significant ( P=0.003). Correlation analysis showed that LRRC55 mRNA expression level was related to tumor differentiation and CEA, but not correlated with patients′ age, gender, tumor location and size, CA19-9 level, lymphatic metastasis and TNM staging. Conclusions:Pancreatic cancer tissue and cell lines had abnormal methylation of LRRC55 gene; LRRC55 gene hypermethylation was related with its lower mRNA expression level in pancreatic cancer, which was correlated with the tumor differentiation and CEA level. LRRC55 may be a potential suppressor gene for pancreatic cancer.
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Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
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Humans , Colorectal Neoplasms , Liver/pathology , Lung/pathology , Prospective Studies , Radiosurgery/methodsABSTRACT
Objective:The medical-related patent transformation level is relatively low in China for a long time. However, with the support and advancement of a series of national policies, domestic patents and other medical intellectual property projects are increasing year by year, and medical transformation is also receiving more and more attention. Zhongshan Hospital affiliated to Fudan University actively promotes the transformation of hospital patents through various channels, and actively explores how to carry out patent transformation and how to improve the success rate of transformation. This article aims to analyze and explore the feasibility of multi-channel promotion of patents, and to open up a new path for the use of new media to promote patent conversion.Methods:Through Excel analysis of " Zhongshan Patent Hero Post" WeChat public account and official Weibo platform weekly page views data and patent salon project data, as well as the patent application and transformation of Zhongshan Hospital in the past 6 years, and analyze the effect of patent promotion.Results:Through multiple channels and various links of effective promotion methods, the patent application and conversion situation of Zhongshan Hospital has doubled in the past 6 years.Conclusions:The hospital will further actively explore the patent application and transformation process, the full-cycle promotion method of each link, and provide a transfer and transformation consulting docking and promotion platform for the scientific research results or patent technologies related to hospitals and enterprises, and help the transformation of medical patents.
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Objective:To investigate the clinical efficacy and safety of balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS) for esophageal varices in patients with cirrhosis.Methods:From December 2020 to April 2021, cirrhotic patients with esophageal varices who planned to receive endoscopic treatment in the Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University were selected and randomly divided into the trial group (treated with bc-EIS) and the control group [treated with endoscopic variceal ligation (EVL)] through computer randomization. The varices eradication rate, rebleeding rate and postoperative adverse reactions in the two groups were studied.Results:During the study, 93 cases were initially included according to inclusion criteria, among which 9 cases were excluded by exclusion criteria. Finally, 84 cases were included for data analysis, with 42 cases in each group. The esophageal varices eradication rate after the first treatment in the trial group was 88.10% (37/42), which was significantly higher than that in the control group [33.33% (14/42)] ( χ2=26.40, P<0.001). The esophageal varices eradication rate after 1 to 2 times and 1 to 3 times of treatment in the trial group were both significantly higher than those in the control group [97.62% (41/42) VS 40.48% (17/42), χ2=29.47, P<0.001; 100.00% (42/42) VS 45.24% (19/42), P<0.001]. The maximum follow-up period was 6 months, and none of the patients had rebleeding in the trial group, and the rebleeding rate in the control group was 4.76% (2/42) ( P=0.494). The incidence of thoracic and abdominal discomfort, nausea and vomiting, and abdominal distension in the trial group and control group were 26.19% (11/42) and 35.71% (15/42) ( χ2=0.51, P=0.474), 2.38% (1/42) and 7.14% (3/42) ( χ2=0.26, P=0.608), and 4.76% (2/42) and 11.90% (5/42) ( χ2=0.62, P=0.430), respectively. No other adverse events such as infection, dysphagia, perforation, esophageal tracheal fistula, esophageal stenosis, or ectopic embolism occurred in any group. Conclusion:Bc-EIS is effective and safe for the treatment of esophageal varices in patients with cirrhosis, with a one-time varices eradication rate of more than 85%, and can be completely eradicated after 1 to 3 times of treatment.
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Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.
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Neoadjuvant chemoradiotherapy combined with total mesorectal excision is the standard treatment for stage T 3-T 4/N+ locally advanced rectal cancer (LARC). However, proctectomy is burdened with consistent postoperative morbidity, severely affecting the quality of life. "Organ preserving" methods could achieve similar oncological outcomes in highly selected patients whose tumors demonstrate (almost) clinical complete response to neoadjuvant treatment, while maintaining the quality of life and anorectal function by keeping the anus. This article aims to summarize the strategies of organ preservation after neoadjuvant treatment of LARC, salvage treatment for regrowth or recurrence, and anorectal function after organ preservation strategies.
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Lateral pelvic lymph node (LPLN) metastasis is a poor prognostic factor for rectal cancer, which is more common in low site, T 3-T 4 stage, and positive lymph nodes in mesorectum. However, there is no accurate predictor of metastasis. At present, high-resolution MRI is the optimal diagnosis of LPLN metastasis, but the threshold value is still unclear. The treatment mode of LPLN metastasis in locally advanced rectal cancer is controversial worldwide. European and American countries advocate chemoradiotherapy combined with total mesorectal resection, while Japan recommends total mesorectal resection combined with LPLN dissection. The combination of radiotherapy and surgery could achieve good local control. Further more, by using the information of lateral lymph nodes before and after radiotherapy, patients with high risk can be screened for intensive treatment, such as LPLN dissection or dose-escalation approaches. Currently, there is still a lack of high-quality evidence on the efficacy of various approaches in the treatment of LPLN metastasis, and more research is needed to improve the treatment strategies.
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Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.
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Objective:To explore the impacts of comprehensive geriatric assessment (CGA) on setup errors during the radiotherapy of elderly patients with rectal cancer.Methods:A total of 45 patients over 70 years of age and receiving radiotherapy were enrolled in the study. A comprehensive geriatric assessment was conducted before the radiotherapy. The enrolled patients had a median age of 77 years, including 28 male and 17 female cases. Meanwhile, 31 patients were determined to be in a good CGA status and 14 were determined to be in a poor CGA status, and 35 patients received radiotherapy in the prone position and 10 in the supine position. Cone beam CT (CBCT) was used for setup correction during radiotherapy. CBCT was performed daily in the first week and once a week from the second week. By fusing and aligning the CBCT images with simulation CT images according to the lumbar vertebra, setup errors in the left-right ( x axis), cranio-caudal ( y axis), and anterior-posterior ( z axis) directions were obtained. A total of 338 CBCT images were obtained. A generalized linear model was used to evaluate the effects of multiple factors on the setup errors. Results:During the radiotherapy, setup errors of all patients were (0.24±0.19) cm in the left-right direction, (0.33±0.25) cm in the cranio-caudal direction, and (0.19±0.15) cm in the anterior-posterior direction. The setup error in the cranio-caudal direction was more than that in the left-right direction and that in the anterior-posterior direction ( Z=-4.86, -7.72, P< 0.001). The setup error in the left-right direction was greater than that in the anterior-posterior direction ( Z=-2.79, P=0.005). The mean setup errors of the good and poor status groups in the left-right direction were (0.21 ± 0.17) and (0.30 ± 0.22) cm, respectively ( Z=2.16, P=0.031). There was no statistically significant difference in the setup errors between cranio-caudal direction and anterior-posterior direction ( P>0.05). The setup errors in the anterior-posterior direction were (0.17 ± 0.13) and (0.27 ± 0.19) cm, respectively for the prone and supine positions during the radiotherapy ( Z=2.85, P=0.004). There was no statistically significant difference in the setup errors between the left-right direction and the cranio-caudal direction ( P>0.05). Conclusion:The status of CGA elderly patients with rectal cancer affects the setup error in the left-right direction. It may be necessary to clinically adjust the PTV margin.
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Major depressive disorder （MDD） is an affective disorder characterized by significant and long-lasting depression， hypoactivity， and thinking and cognitive retardation. Some patients may conduct self-hram or suicide and have delusion， hallucination， and other mental symptoms. MDD is believed to be correlated with brain and heart， but there is no complete theory or mechanism fully explaining the pathogenesis of MDD. Traditional Chinese medicine （TCM） holds that the brain and heart dominate the formation of and change in mind， and MDD falls into the category of mental disease. It is mainly diagnosed as depression， visceral agitation， or Lily disease. Triple energizer is a key zang-fu organ that governs Qi transformation. There has always been some controversy about its anatomical structure. In recent years， important progress has been made in the research on the substantive structure of triple energizer. It is found that the structure and function of triple energizer are highly consistent to those of "mesenchyme"， a fluid space supported by a complex network of collagen fibers and widely distributed throughout the body. Different from known tissues and organs， it is a large organ responsible for information communication， material exchange， and energy metabolism. The triple energizer is partially contained in the structure of brain and heart and connects with the brain and heart， thus forming a "brain-heart-triple energizer" system with close physiological and pathological connections. With the association of "brain-heart-triple energizer" as the basis and Qi transformation as the core link， this paper elucidated the pathogenesis of MD and put forward that MDD resulted from "brain and heart Yang deficiency and Qi depression due to triple energizer obstruction"， so as to improve TCM understanding of the pathogenesis of MDD and perfect the TCM theories of encephalopathy and triple energizer.
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PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.