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Objective:To explore the effects of Alpha-2-macroglobulin-rich serum (A2MRS) on knee post-traumatic osteoarthritis (PTOA).Methods:The knee PTOA models were constructed by transection of the anterior cruciate ligament (ACL) in 80 SD male rats, aged 2 months and weighing from 250 to 300 g, which were randomized into 4 groups ( n=20): a high dose group (A2MRS containing 20 μg/μL A2M administered), a low dose group (A2MRS containing 10 μg/μL A2M administered), a positive control group (normal saline administered), and a blank control group (the knee joint cut pseudooperatively and normal saline administered). HE, toluidine blue staining, safranine O staining, modified Mankin scoring and Osteoarthritis Research Society International (OARSI) scoring were conducted to evaluate and compare the therapeutic effects of A2MRS on the knee PTOA among the 4 groups. Results:The rat cartilage was thinner with patchy and cracked surface, and the chondrocytes were reduced and distributed unevenly in the positive control group, compared with the blank control group. The modified Mankin score (3.89±0.93) and OARSI score (10.05±0.72) in the positive control group were significantly higher than those in the blank control group (0.67±0.07 and 3.10±0.29) ( P<0.05). The rat cartilage was thicker with basically complete and crack-free surface, and the chondrocytes were increased and distributed more evenly in the high dose group and the low dose group, compared with the positive control group. The modified Mankin scores (1.33±0.50 and 1.56±0.53) and OARSI scores (6.30±0.64 and 4.75±0.66) in the high dose group and the low dose group were significantly lower than those in the positive control group ( P<0.05). However, there were no such differences between the high dose group and the low dose group ( P>0.05). Conclusion:A2MRS effectively delays the pathological process of knee PTOA.
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Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.
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Ionizing radiation can induce the death of lymphatic endothelial cells, leading to structural damage, dysfunction, and reduction of lymphatic vessels, which poses a negative impact on radiotherapy. However, it can also induce tumor cells and tumor-infiltrated immune cells to secrete various cytokines and promote tumor-associated lymphangiogenesis, which favors anti-tumor therapy and improve anti-tumor immunity. Studying the changes in lymphatic vessels after ionizing radiation may be a way to explore the synergistic anti-tumor effects of radiotherapy and immunotherapy. This review summarized the morphological changes in lymphatics after ionizing radiation, the molecular mechanisms for the effects of ionizing radiation on lymphatic vessels, and the clinical value of lymphatic changes after ionizing radiation, aiming to provide ideas for the study of the effects of ionizing radiation on lymphatic vessels.
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In recent years, heavy ion beams have received great attention in the field of malignant tumor radiotherapy due to their radiation physics and biological characteristics. The high rate of local tumor control is one of its advantages, but the control rate of metastatic lesions is still crucial in the treatment of most malignant tumors. Clinical studies on the combined conventional radiotherapy and immunotherapy suggest that the combination of the two can not only control the primary lesions, but may also reduce or completely eliminate distant metastatic lesions. High linear energy transfer radiation, especially heavy ion beams, may have stronger potential in combined immunotherapy. Therefore, this article focuses on the basic research progress of heavy ion beams regulating anti-tumor immune effects and their combined application with immunotherapy.
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Inguinal incarcerated hernia in adults is a common acute abdomen in hernia and abdominal wall surgery. If not treated in time, it is easy to progress to constrictive hernia, lead to intestinal ischemic necrosis, cellulitis of tegmental tissue outside the hernia, hernia sac empyema, intestinal fistula, and even cause toxic shock, with significantly increased mortality. The types of incarceration are different and the corresponding management methods are different. Based on the proposal of the concept of musculopubic foramen hernia repair, inguinal incarcerated hernia includes incarcerated indirect hernia, incarcerated direct hernia, incarcerated femoral hernia, etc. At present, there is no uniform standard for the comprehensive treatment of different types of inguinal incarcerated hernia, and the clinical management strategies of adult inguinal incarcerated hernia still face serious challenges.
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Objective To explore the high-risk factors of metabolic bone disease (MBD) in premature infants by retrospective analysis of the clinical data so as to provide evidence for optimal clinical management. Methods Clinical data of premature infants with birth weight<1500 g admitted in our hospital from January 2016 to December 2017 were retrospectively analyzed. Infants with serum alkaline phosphatase ( ALP )>500 IU/L and blood phosphorus <1. 5 mmol/L were selected as MBD group and premature infants with birth weight <1500 g were selected randomly as non-MBD group. General data, pulmonary surfactant, continuous positive airway pressure, mechanical ventilation, start time of enteral nutrition, parenteral nutrition ( PN) time, breast feeding time and breast milk fortifier adding, drug usage, hospitalization time and complications were re-corded and compared between the two groups. Results A total of 440 premature infants with birth weight<1500 g were admitted to the hospital during the study period. 58 [ 13. 2％ ( 58/440) ] infants were enrolled in the MBD group, among which infants with birth weight<1000 g accounting for 56. 9％ ( 33/58) . High birth weight (OR=0. 62, 95％ CI:0. 389-0. 990) was an independent protective factor of MBD in premature in-fants. The higher the birth weight, the lower the risk of MBD in premature infants. The longer duration of breast feeding time ( OR= 2. 191, 95％ CI:1. 628-2. 950) , later initial time of enteral feeding ( OR=2. 695, 95％CI:1. 710-4. 248), longer duration of PN (OR=6. 205, 95％ CI:3. 359-11. 463) time, longer duration of respiratory supporting time ( OR=1. 046, 95％ CI:1. 026-. 067) , longer hospital stay time ( OR=1. 703, 95％ CI:1. 109-2. 615) and small for gestational age ( OR=2. 965, 95％ CI:1. 163-5. 658) were inde-pendent risk factors of MBD in premature infants. The duration of PN was the most important independent risk factor of MBD in premature infants (OR=6.205, 95％ CI: 3.359-11.463). Conclusion Multiple factors can lead to MBD of premature infants. The high birth weight is an independent protective factor of MBD and the duration of PN is the most important independent risk factor of MBD in premature infants.
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Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.
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Objective To observe the changes in cytoskeleton (CSK) and glycosaminoglycan (GAG) synthesis following passage culture of articular chondrocytes and the correlation between CSK and GAG.Methods Eight male New Zealand White rabbits (8-month-old) were sacrificed by air embolism.After the chondrocytes from their knee joints were isolated by enzymolysis method,monolayer culture was performed.The chondrocytes of primary passage (P0) and passages 1 & 2 (P1,P2) were inoculated into 24-well plates with round cover slips put at the bottoms.Cell climbing slices were fixed after attachment of chondrocytes.The CSK proteins,actin,vimentin,tubulin and vinculin were stained by immuuofluorescence antibody on P0,P1 and P2 cell climbing slices,respectively.The CSK morphology was observed by laser confocal scanning microscopy and the fluorescence intensities of CSK proteins were detected by the fluorescence intensity software.The medium was changed for each generation after cell fusion and the GAG concentrations in the supernatants were measured at 24,36,48,60 h after medium change by alcian blue method.Results The intermediate filament networks became loosen and the dense distributions surrounding the nucleus decreased;more microtubule processes formed at the cell periphery with passage.The fluorescence intensity of actin of P1 chondrocytes was significantly increased than that of P0 (P ＜ 0.05),but there were no such significant differences between P0 and P2 or between P1 and P2 (P ＞ 0.05).The fluorescence intensities of vimentin and tubulin were significantly decreased with passage respectively,and there were such significant differences between any two of P0,P1 and P2 (P ＜ 0.05).The GAG concentrations in the supernatants were significantly decreased with passage at each time point,and there were such significant differences between any two of P0,P1 and P2 (P ＜ 0.05).Conclusions Passage culture of articular chondrocytes may lead to changes in morphology and protein expression intensity of the main components of CSK,and accordingly to decreased synthesis amount of GAG,one of the extracellular matrix of chondrocytes,indicating the changed characteristics of chondrocytes after passage and a certain correlation between CSK and GAG.
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Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
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Animals , Female , Humans , Mice , Antibodies, Neoplasm , Pharmacology , Antibodies, Neutralizing , Pharmacology , Breast Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , CD4-Positive T-Lymphocytes , Allergy and Immunology , Pathology , Interleukin-17 , Genetics , Allergy and Immunology , Interleukins , Genetics , Allergy and Immunology , Macrophages , Allergy and Immunology , Pathology , Mammary Neoplasms, Animal , Drug Therapy , Genetics , Allergy and Immunology , Neoplasm Metastasis , Tumor Microenvironment , Genetics , Allergy and ImmunologyABSTRACT
Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood.Radiation therapy has been integrated into the primary treatment of most patients with rhabdomyosarcoma, but which in turn potentially induces severe acute and late toxicities.Proton therapy in recent years has been more and more used in the treatment of rhabdomyosarcoma, which is safe and effective, with no serious adverse events.Compared with conventional photon therapy, proton therapy has distinct physical advantages and enables greater precision in the delivery of tumoricidal radiation doses with reduced irradiation of normal tissues, and improves quality of life for patients.Additional follow-up and prospectively studies are needed to determine whether proton therapy truly reduces the incidence and severity of late effects in comparison to patients treated with modern photon techniques.
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BACKGROUND: Percutaneous vertebroplasty (PVP) is usually used for osteoporotic thoracolumbar fractures,which has various advantages such as easy to operate, short operation time, less trauma, rapid recovery,analgesic effect and so on. But its application is restricted due to nerve compression symptoms and pulmonary embolism caused by bone cement leakage. Thereafter, how to reduce the leakage of bone cement is an issue of concern.OBJECTIVE: To investigate the relationship between the lumbar quantitative computed tomography (QCT) values and contrast agent dispersion in osteoporotic thoracolumbar fractures. METHODS: Sixty cases of osteoporotic thoracolumbar fractures undergoing PVP were enrolled, and received QCT examination before surgery, and contrast agent was injected intraoperatively. X-ray examination was conducted to detect the bone mineral density, contrast agent dispersion and leakage of bone cement, and the relationship between the lumbar QCT values and contrast agent dispersion as well as leakage of bone cement.RESULTS AND CONCLUSION: (1) There were 110 vertebral fractures, and 74 vertebrae with contrast agent diffusing more than vertebral midline, accounting for 67.3%. There was significant difference in the contrast agent dispersion among groups (P 0.05). (3) These results suggest that contrast agent dispersion in osteoporotic thoracolumbar fractures has a certain relationship with the lumbar QCT values, and lumbar QCT values with more contrast agent dispersion, but the lumbar QCT values have no correlation with bone cement leakage. Therefore, choosing a appropriate approach based on the QCT values and contrast agent dispersion can reduce leakage and improve the safety of PVP.
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Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three?dimensional radiotherapy ( 3DRT) for stage IV non?small cell lung cancer ( NSCLC) . Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum?based doublets chemotherapy, with a median number of chemotherapy cycles of 4( 2?6 cycles) and a median dose of 3DRT of 60?3 Gy (36?0?76?5 Gy).The Kaplan?Meier method was used to calculate overall survival ( OS) rates, the log?rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1?, 2?, and 3?year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11?500?14?500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale ( KPS) after treatment significantly prolonged OS ( P=0?000,0?022,0?003, and 0?029) , and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0?058 and 0?075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS ( all P<0?05) . Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials. gov, registration number:ChiCTRTNC10001026.
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Objective To assess the efficacy and safety of the carbon ion radiotherapy for stage Ⅰ non-small cell lung cancer (NSCLC).Methods We searched multiple electronic bibliographic databases,including the Cochrane library,PubMed,EMBASE,China Journal Full-text Database,Chinese Biomedical Database,and the Wanfang Database to assemble the available studies of carbon ion radiotherapy for stage Ⅰ non-small cell lung cancer.MetaAnalyst Beta 3.13 and STATA 12.0 software were used to combine the extracted data.Results Ten studies (seven trials) were included.The overall survival rates of 1,3 and 5 years were 95.1％,68.5％ and 45.9％,respectively.The local control rates of 1,3 and 5 years were 90.2％,76.7％ and 81.2％,respectively.The cause specific survival rate of 1,3 and 5 years were 82.9％,58.5％ and 57.3％,respectively.The rate of primary recurrence and total recurrence were 45.8％ and 11％,respectively.The rates of total death and death from lung cancer were 52.4％ and 28.3％,respectively.There were differences observed between T1 stage and T2 stage in regards to five year overall survival rate,total recurrence,lung cancer death,and grade 1 and grade 2 skin toxicities.Conclusions Available data demonstrate that carbon ion radiotherapy,in general,is a safe and feasible treatment modality for stage Ⅰ NSCLC.Although current results are promising,more evidence is required before carbon ion radiotherapy can become the international standard treatment for lung cancer patients.
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Objective To evaluate the efficacy of the carbon ion radiotherapy for prostate cancer by Meta-analysis.Methods We searched the Cochrane library,PubMed,EMBASE,China Journal Fulltext Database,Chinese Biomedical Database,and Wanfang Database from their inception to December 2015,in order to collect clinical trial data of carbon ion radiotherapy for prostate cancer.References included within these studies were also retrieved.Meta-analysis was performed using MetaAnalyst Beta 3.13 and STATA 12.0 software.Results Six studies (eight clinical trials) were included.The results of Meta-analysis show that,the overall survival rates of 3,4,5 and 8 years were 95.7％,90.9％,91.8％ and 83.9％,respectively.The cause specific survival rate of 4 and 5 years were 97.1％ and 97.6％.The bNED rate of 3,4,5 and 8 years were 88％,86.3％ and 79.1％,respectively.The local control rates of 3,4 and 5 years were 98.1％,97.1％ and 98.4％,respectively.The rate of total death,prostate cancer death and intercurrent death were 7％,2.4％ and 7％,respectively.Different T-stage may affect the fiveyear of overall survival rate,bNED rate and cause specific survival rate.Conclusions The current evidence shows that carbon ion radiotherapy in gcncral is a fcasiblc trcatmcnt for prostate cancer,whether carbon ion is better than other radiotherapy,prospective,randomized,controlled clinical trial to get more evidence is required for carbon ion radiotherapy versus standard treatment for prostate cancer patients.
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This study was designed to investigate the impact of ultra-filtration extract mixture from Astragals mongholicus (UEMAM) o radiosensitivity of H22 ascitic tumor in mice to 12C6+ ions radiation. The H22 ascitic tumor model was established in mice by intraperitoneal injection of 0.2 mL H22 ascitic cells. The animals were subsequently divided into 4 groups randomly, treated with normal saline, UEMAM, heavy ion beam radiotherapy and UEMAM plus heavy ion beam radiotherapy, respectively. The body weights, abdomen circumference of the mice were measured and the mouse behavior was monitored every day; survival time was recorded to evaluate life extension effect; flow cytometry technique was used to detect H22 cell apoptosis and cell cycle; protein levels of p53, Bax, Bcl-2 and cleaved Caspase-3 were analyzed by Western blot; the single cell gel electrophoresis was used to detect the level of deoxyribonucleic acid damage (DNA damage). The results suggest that UEMAM significantly increased survival time, and decreased body weights and abdomen circumference over the saline control group. The treatment increased cell apoptosis, cycle arrest and DNA damage compared to the saline control group. UEMAM significantly enhanced the therapeutic effect of heavy ion beam radiation in survival time, and decreased body weights and abdomen circumference in the tumor-baring mice. The combination increased cell apoptosis, cycle arrest and DNA damage compared to the radiotherapy group. The results of Western blot suggest that the treatment significantly enhanced p53-induced apoptotic signals. The experiment discovered that UEMAM could improve radiosensitivity of H22 ascitic tumor through activation of p53-mediated apoptotic signal pathway.
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Objective To investigate the efficacy and safety of three?dimensional radiotherapy (3DRT) with concurrent chemotherapy for stage IV non?small?cell lung cancer ( NSCLC). Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status ( KPS) score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease (≤3 organs). Survival rates and acute toxicities in those patients were evaluated. Results The 3?year follow?up rate was 98?? 5% and the 3?year sample size was 165. The median overall survival (OS) and progression?free survival (PFS) were 13?? 0 months (95% CI,11?? 7 ?14?? 3 months) and 9?? 0 months (95% CI,7?? 7 ?10?? 3 months), respectively, while the 1?, 2?, and 3?year OS rates were 53?? 5%, 15?? 8%, and 9?? 2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3 , a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time ( P=0?? 008;P= 0?? 010;P= 0?? 014). The incidence rates of grade 3?4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37?? 9%, 10?? 1%, 6?? 9%, 2?? 5%, and 6?? 6%, respectively. The main cause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number:ChiCTRC10001026.
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Internal mammary nodes are part of the first stop of mammary gland lymphatic drainage.It plays an important role in the process of occurrence and development of breast cancer.Whether irradiation internal mammary nodes or not is still a larger controversy.At present,for the early stage patients,the efficacy of internal mammary lymph node irradiation is not clear.For the patients with positive axillary lymph nodes,inboard or central quadrant lesions,postoperative radiotherapy of internal mammary nodes has a certain value.
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Malignant gliomas cells grow invasively with no clear boundary,and a complete resection surgery is very difficult,and the pathological type is not sensitive to radiotherapy and chemotherapy,so the overall treatment effect is not ideal,and this disease is very prone to local recurrence after treatment.The treatment of malignant glioma is mainly composed of surgical resection with postoperative radiotherapy and chemotherapy.Other new treatments include targeted therapy,immune therapy,gene therapy and so on.
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Objective To assess the efficacy and safety of intensity-modulated radiation therapy (IMRT) for nasopharyngeal neoplasm.Methods PubMed,EMBASE,Cochrane Library,CBM,CNKI,VIP and WanFang Data were fully searched up from creating database to June 15,2012.Randomized controlled trials (RCTs) of IMRT versus conventional radiotherapy (CRT) for nasopharyngeal neoplasm were included.The quality of included studies was evaluated by two individual researchers and data were analyzed by using RevMan 5.1 software.Results Fifteen RCTs were included.Meta-analyses suggested that patients treated by IMRT had a higher fractional stimulated parotid salivary flow rate and a higher stimulated whole salivary flow rate than CRT.IMRT can significantly reduce the acute xerostomia (RR =0.46,P ＜ 0.000 1),reaction of mucosa(RR =0.g6,P =0.04),reaction of skin (RR =0.33,P ＜ O.000 1),long-dated xerostomia (RR ＝0.28,P =0.01) and limitation of mouth opening (RR =0.42,P =0.008).And IMRT trended to improve short-term efficacy (RR =1.22,P =0.02) and long-term survival (RR =1.25,P =0.04).Moreover,IMRT trended to shorten the treatment time while increasing the costs.Conclusion Compared with CRT,IMRT trends to be superior for nasopharyngeal neoplasm.However,because of small sample size,the results need to be proved by more clinical trials.
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10.3969/j.issn.2095-4344.2013.26.021