ObjectiveTo investigate the intervention effect of Tengli Kangliu prescription （TKP） on the carcinogenesis of colorectal adenoma （CRA） induced by azoxymethane （AOM）/dextran sulphate sodium salt （DSS） in C57BL/6 mice and decipher the potential mechanism through regulating the signal transducer and activator of transcription 3 （STAT3） pathway to target M2-type macrophages. MethodsA total of 55 male C57BL/6 mice were randomized into a blank group （n=10）， a model group （n=15）， a celecoxib （0.02 g·kg^-1·d^-1） group （n=15）， a TKP （42.43 g·kg^-1·d^-1） group （n=15）. The mice in the model， TKP， and celecoxib groups were modeled for CRA lesions through the AOM/DSS three-cycle protocol. The intervention in each group began one week after free access to DSS and lasted for 12 weeks， and the blank group received 20 mL·kg^-1·d^-1 normal saline through gavage. Throughout the study period， changes in body mass and survival rate were recorded， alongside measurements of colorectal length and spleen mass. Histological changes of the colonic tissue were observed by HE staining. Immunohistochemical （IHC） staining was performed to detect the positive expression of CD68 and CD11c in the colorectal tissue. Western blot was employed to assess the protein levels of STAT3， phosphorylated （p）-STAT3， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the intestinal tissue. Real-time quantitative PCR was employed to analyze the mRNA levels of arginase 1 （Arg1）， CD206， and vascular endothelial growth factor （VEGF）. Enzyme-linked Immunosorbent assay（ELISA） was employed to measure the serum concentrations of Th2-type cytokines interleukin （IL）-4， IL-6， and IL-13 in mice. ResultsCompared with the blank group， the model group exhibited symptoms including diarrhea， hematochezia， and body mass loss， accompanied by shortened colon length， mucosal damage， and multiple tumors. In addition， the model group showcased up-regulated protein levels of STAT3， p-STAT3， and Bcl-2， down-regulated protein level of Bax， increased positive expression of CD68 and CD11c， and up-regulated mRNA levels of Arg1， CD206， and VEGF in the colon tissue， together with elevated serum levels of IL-4， IL-13， and IL-6 （P<0.05）. Compared with the model group， the above-mentioned indicators were partially reversed in both TKP group and celecoxib group， with superior effects observed in the TKP group （P<0.05）. ConclusionTKP significantly improves the survival quality of the mouse model of AOM/DSS-induced CRA by reducing intestinal inflammation and decreasing colorectal tumor number and size. It may delay the progression of AOM/DSS-induced colorectal tumor-like lesions by inhibiting activation of the STAT3/p-STAT3 signaling pathway in the intestinal tissue， targeting regulation of M2-type macrophages， and improving the tumor microenvironment， thereby suppressing CRA carcinogenesis.

Objective To explore the predictive factors of recurrence of chronic suppurative otitis media(CSOM)after otoendoscopic surgery,and construct a risk quantified nomogram model.Methods The clinical data of 485 patients with CSOM who underwent otoendoscopic surgery in our hospital from February 2021 to February 2023 were retrospectively analyzed.The patients were divided into the recurrence group and the non-recurrence group according to the recurrence situation during the follow-up period.The clinical data of patients between the two groups were compared,and the predictive factors of postoperative recurrence were analyzed by Cox regression method.A risk quantified nomogram model was constructed based on these predictive factors.The predictive efficiency of the model was verified by receiver operating characteristic(ROC)curve,and the calibration degree of the model was verified by Hosmer-Lemeshow goodness of fit analysis,and the clinical net benefit of the model was evaluated by decision curve analysis(DCA)method.Results Follow-up ranged from 6 to 39 months,with a median of 21(11,32)months,the postoperative recurrence rate was 14.64%(71/485).Combined with recurrent upper respiratory tract infections(HR=3.019,95%CI:1.609 to 5.664),combined with chronic rhinosinusitis(HR=2.428,95%CI:1.529 to 3.856),combined with adenoid hypertrophy(HR=2.214,95%CI:1.381 to 3.551),middle ear risk index(MERI)score(HR=2.863,95%CI:1.445 to 5.675),the seven-item eustachian tube dysfunction questionnaire(ETDQ-7)score(HR=2.679,95%CI:1.505 to 4.765)and inadequate drainage of the surgical cavity(HR=2.373,95%CI:1.503 to 3.746)were the risk factors for postoperative recurrence(P<0.05).A risk quantified nomogram model of recurrence after otoendoscopic surgery in CSOM patients was constructed based on the predictive factors of Cox regression analysis,among them the risk value ranges of patients who combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score,and inadequate drainage of the surgical cavity were 0 to 65 points,0 to 56 points,0 to 52 points,0 to 76 points,0 to 64 points,and 0 to 76 points,respectively.The area under the curve of ROC,sensitivity and specificity of the model for predicting postoperative recurrence were 0.928(95%CI:0.875 to 0.948),85.92%and 88.89%,respectively.There was no significant difference between the predicted probability of postoperative recurrence and the actual probability(P>0.05).The threshold probability of postoperative recurrence predicted by the model in the range of 4%to 92%could obtain clinical net benefit.Conclusion The predictive factors of recurrence after otoendoscopic surgery in CSOM patients include combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score and inadequate drainage of the surgical cavity,the risk quantified nomogram model based on these factors is highly effective in predicting postoperative recurrence.

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P＜0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P＜0.05),and significantly positively correlated with DFI and HDS(P＜0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR％,DFI and HDS among mild,moderate and severe varicocele groups(P＜0.05).Seminal plasma nORP,sperm concentration,PR％and DFI in severe group were significantly lower than those in mild and moderate groups(P＜0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P＜0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P＜0.05).And PR％in varicocele group was significantly lower than that in control group(P＜0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.

Objective To explore the predictive factors of recurrence of chronic suppurative otitis media(CSOM)after otoendoscopic surgery,and construct a risk quantified nomogram model.Methods The clinical data of 485 patients with CSOM who underwent otoendoscopic surgery in our hospital from February 2021 to February 2023 were retrospectively analyzed.The patients were divided into the recurrence group and the non-recurrence group according to the recurrence situation during the follow-up period.The clinical data of patients between the two groups were compared,and the predictive factors of postoperative recurrence were analyzed by Cox regression method.A risk quantified nomogram model was constructed based on these predictive factors.The predictive efficiency of the model was verified by receiver operating characteristic(ROC)curve,and the calibration degree of the model was verified by Hosmer-Lemeshow goodness of fit analysis,and the clinical net benefit of the model was evaluated by decision curve analysis(DCA)method.Results Follow-up ranged from 6 to 39 months,with a median of 21(11,32)months,the postoperative recurrence rate was 14.64%(71/485).Combined with recurrent upper respiratory tract infections(HR=3.019,95%CI:1.609 to 5.664),combined with chronic rhinosinusitis(HR=2.428,95%CI:1.529 to 3.856),combined with adenoid hypertrophy(HR=2.214,95%CI:1.381 to 3.551),middle ear risk index(MERI)score(HR=2.863,95%CI:1.445 to 5.675),the seven-item eustachian tube dysfunction questionnaire(ETDQ-7)score(HR=2.679,95%CI:1.505 to 4.765)and inadequate drainage of the surgical cavity(HR=2.373,95%CI:1.503 to 3.746)were the risk factors for postoperative recurrence(P<0.05).A risk quantified nomogram model of recurrence after otoendoscopic surgery in CSOM patients was constructed based on the predictive factors of Cox regression analysis,among them the risk value ranges of patients who combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score,and inadequate drainage of the surgical cavity were 0 to 65 points,0 to 56 points,0 to 52 points,0 to 76 points,0 to 64 points,and 0 to 76 points,respectively.The area under the curve of ROC,sensitivity and specificity of the model for predicting postoperative recurrence were 0.928(95%CI:0.875 to 0.948),85.92%and 88.89%,respectively.There was no significant difference between the predicted probability of postoperative recurrence and the actual probability(P>0.05).The threshold probability of postoperative recurrence predicted by the model in the range of 4%to 92%could obtain clinical net benefit.Conclusion The predictive factors of recurrence after otoendoscopic surgery in CSOM patients include combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score and inadequate drainage of the surgical cavity,the risk quantified nomogram model based on these factors is highly effective in predicting postoperative recurrence.

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, β-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.
Abdominal Pain/complications* ; Adult ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Anticoagulants ; Arrhythmias, Cardiac/complications* ; China/epidemiology* ; Diuretics ; Dizziness/complications* ; Dyskinesias/complications* ; Electrocardiography ; Europe/epidemiology* ; Female ; Humans ; Hypotension/complications* ; Middle Aged ; Platelet Aggregation Inhibitors ; Stroke Volume ; Takotsubo Cardiomyopathy/etiology* ; Ventricular Function, Left

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.
Colorectal Neoplasms ; Humans ; Liver/pathology* ; Lung/pathology* ; Prospective Studies ; Radiosurgery/methods*