Objective:To explore the amplitude of normal kidney motion in the 3D direction and its influencing factors under free-breathing condition.Methods:Clinical data of 28 patients with a KPS score≥80 who received 4D CT scan from March 2018 to March 2019 were collected. All patients were diagnosed with liver, pancreatic or lung tumors. The kidney was outlined and the geometric center and 3D coordinate values were recorded. The motion of bilateral kidneys in each direction and the 3D direction was calculated. The volume of kidney and surrounding organs, age, sex, height and body mass index (BMI) were recorded. Clinical data were statistically compared by t-test or nonparametric test. Results:The motion of the left and right kidneys in the the sup-inf (SI) direction were the largest up to (8.39±3.18) mm and (7.71±3.55) mm. The motion amplitudes of bilateral kidneys in male patients were significantly larger than those of the female counterparts in the left-right (LR), SI and 3D directions (all P<0.05). The motion amplitudes of bilateral kidneys in patients taller than 165 cm were significantly larger than those of their counterparts with a height of ≤165 cm (all P<0.05). Patients with a BMI≥25 kg/m 2 had significantly larger motion amplitudes of the left kidney in the LR and ant-post (AP) directions compared with those of normal weight counterparts (all P<0.05). The motion amplitude of the left kidney in the AP direction in patients with the left kidney volume of >180 cm 3 was significantly larger than that of patients with smaller left kidney volume ( P=0.014). Age was not significantly associated with kidney motion in each direction ( P>0.05). Conclusions:Kidney motion mainly occurs in the SI direction. The kidney motion amplitudes in male and taller patients are larger. Special attention should be paid to the use of breath motion control device to decrease the normal tissue damage.

OBJECTIVE: To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the anti-tumor activity of the drug-loaded micelles. METHODS: CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. RESULTS: FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 μg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. CONCLUSIONS FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.
Antineoplastic Agents ; Chitosan ; Doxorubicin ; Drug Carriers ; Folic Acid ; Humans ; Micelles ; Nanostructures ; Polymers

Objective:To analyze the influencing factors of hemoglobin changes in prostate cancer patients during radiotherapy combined with androgen-deprivation therapy (ADT) and analyze the relationship between the hemoglobin changes and long-term prognosis.Methods:The changes of hemoglobin levels in 145 prostate cancer patients treated with radiotherapy combined with ADT in Department of Radiation Oncology of Peking University First Hospital from November 2011 to May 2015 were retrospectively analyzed. Intensity-modulated radiotherapy (IMRT) was employed for conventionally fractionated radiotherapy. Luteinizing hormone-releasing hormone agonist was utilized for endocrine therapy.Results:The median hemoglobin reduction during radiotherapy combined with ADT was 8 g/L. The higher the baseline level of hemoglobin, pelvic irradiation and GS score before radiotherapy, the more obvious the decrease of hemoglobin during treatment (all P<0.001). Pelvic radiotherapy significantly increased the decline tendency of hemoglobin throughout the combined treatment (86.8% vs. 72.8%, P=0.05). The duration of endocrine therapy before radiotherapy and the hemoglobin changes during endocrine therapy alone were not significantly correlated with the degree of hemoglobin decline during subsequent radiotherapy ( P=0.53 and 0.837). The biochemical failure-free survival did not significantly differ between patients with significant and mild hemoglobin reduction ( P=0.686). Conclusions:The baseline level of hemoglobin before radiotherapy is negatively correlated with the decrease of hemoglobin during combined therapy. Pelvic radiotherapy is positively correlated with hemoglobin reduction during combined therapy. Hemoglobin reduction during combined therapy is not associated with the long-term biochemical failure-free survival of patients.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Sarcopenia, referred to as myopenia, is a systemic syndrome characterized by decreased muscle mass and muscle strength, and decline of motor function.The elderly are a high incidence group of myopenia.With the aging of the world's population becoming increasingly severe, the incidence rate of sarcopenia has also increased, which has brought a heavy burden to the elderly family and society, and has become an important social health problem for the elderly.At present, there are more and more researches on sarcopenia, but the pathogenic factors of sarcopenia are complex and diverse.The prevention and treatment of sarcopenia still need to be further explored and studied.The establishment of an ideal animal model is the key premise and basis for the related research of sarcopenia.In this paper, the different modeling methods, advantages and disadvantages as well as the scope of application of sarcopenia animal models are described, which can provide reference and help for the subsequent animal experimental research of sarcopenia.

Objective:To investigate the efficacy and safety of radiotherapy for all metastases in patients with metachronous oligo-metastatic prostate cancer after radical treatment.Methods:From October 2011 to February 2021, 41 patients with prostate cancer with less than 5 metastases after radical treatment were retrospectively analyzed in a single center. The median age at radiotherapy was 68 (57-81) years. Forty patients (98%) received androgen deprivation therapy (ADT). There were 28 patients in the hormone sensitive (HSPC) group and 13 patients in the hormone resistant (CRPC) group. The median initial PSA was 24.4 (7.4-399.0) ng/ml. Tumor stage: T 2 stage 11 patients, T 3 stage 27 patients, T 4 stage 3 patients.30 patients were in N 0 stage and 11 patients in N 1 stage. Gleason score was 7 in 12 patients, 8 in 9 patients, 9 in 18 patients, and 10 in 2 patients.33 patients were treated with surgery, and 8 patients were treated with radiotherapy. The time span from diagnosis to metastasis was 3.1 (0.2-1.8) years. Conventional imaging examination (CT/ MRI/bone scan) before radiotherapy was used in 7 patients, and PSMA PET/CT examination was used in 34 patients.The median PSA before radiotherapy was 1.3(0.1-33.8) ng/ml. There were 62 metastases in 41 patients, including 1 lesion in 28 patients, 2 lesions in 9 patients, 3 lesions in 2 patients, and 5 lesions in 2 patients. Fifty-four patients had bone metastases and eight had retroperitoneal lymph node metastases. Twenty-two bone metastases were located in the pelvis, 18 in the vertebral body, 12 in the ribs, one in the femur and one in the sternum.The median metastatic volume was 5.8(0.2-81.7) cm 3.Daily image-guided rotational intensity modulated radiotherapy was used to cover all metastases.Dose segmentation modes include 37.5Gy/7.5Gy/5F, 60Gy/3Gy/20F, 65-70Gy/2.6-2.8Gy/25F.The median biological effective dose (BED 3) was 120 (67-147) Gy. The primary endpoint was biochemical progression-free survival (BPFS), the secondary endpoints were acute and late toxic side effects, local relapse-free survival (LPFS), and overall survival (OS). Results:The median follow-up time was 21 months (range 5-72 months). All patients completed radiotherapy, and 16 patients had grade 1 to 2 acute toxicity and side effects, and no grade 3 or above acute and late stage side effects. 1-year LPFS was 97.1%.The 1-year and 2-year BPFS were 77.5% and 59.2%, respectively. The median BPFS time was 29 months (range 13.9-44.2 months). Univariate analysis showed that the HSPC group ( P<0.001) and the group with total metastatic volume ≤ 5.8cm 3 ( P=0.010) had higher BPFS. The median BPFS time was 37 months in the retroperitoneal lymph node metastases subgroup and 17 months in the bone metastases subgroup ( P=0.141). In the HSPC group, the median BPFS was 30(22-38) months. After radiotherapy, PSA decreased in all 28 patients, and increased in 6 patients. The median BPFS was 12(4-18) months. In the CRPC group, the median BPFS was 4(0-8) months. PSA decreased in 10 patients (76.9%) after radiotherapy, and PSA decreased in 6 patients. The median BPFS was 5(3-28) months. Three patients’PSA did not decrease after radiotherapy, and they were treated with new endocrine therapy drugs, chemotherapy, immunotherapy and other systemic therapy. Conclusions:For patients with metachronous metastases after radical treatment, full coverage radiotherapy has good safety and high local control rate. HSPC patients and patients with low tumor load could be recommended to receive radiotherapy for all metastatic lesions preferentially, and patients with only retroperitoneal lymph node metastases may have better prognosis after radiotherapy than patients with bone metastases.

Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.

Examining mechanisms involved in the mutual regulation between the muscular system and the skeletal system, elucidating the key issues responsible for loss of muscle and bone mass and strength, and thus halting the progression of these conditions are critical measures for reducing fractures caused by falls and subsequent disability and mortality.At present, most studies have treated the muscular system and the skeletal system separately, often ignoring the mutual regulation and connections between them.This article reviews the current research progress on the mechanisms of interaction between the two systems, aiming to provide a basis for the prevention, diagnosis and treatment of disuse-related diseases in the elderly population.

To prepare a nano-carrier based on combining bacterial outer membrane vesicles (OMV) with three block polymer pluronic F127 (PEO-PPO-PEO) (OMV-F127) and to investigate its immunological activity.Attenuated salmonella (sal) was cultivated. OMV were separated by centrifugal ultrafiltration or ultrasonication, and OMV-F127 was prepared by mechanical extrudation method. The protein contents and compositions were tested with BCA and SDS-PAGE; the morphology of OMV, F127 and OMV-F127 were observed with FM and TEM; the particle sizes and their zeta potential were determined with DLS. Mouse macrophage RAW246.7 cells were treated with OMV-F127 (50 μg/mL, 100 μg/mL) in vitro, and the concentrations of IL-12, TNF-α and IFN-γ in culture supernatant were measured with ELISA kits.The contents of protein in separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL and 2.7 mg/mL, respectively. SDS-PAGE showed the marker protein OmpF/C in OMV. Under the FM and TEM, ball-like structure of F127 and OMV-F127 was observed. Size analysis revealed that the diameters of OMV, F127 and OMV-F127 were 72±2 nm, 90±3 nm and 92±2 nm, respectively. ELISA tests revealed that OMV-F127 significantly stimulated the secretion of IL-12, TNF-α and IFN-γ in RAW246.7 cells.A nano-carrier based on bacterial outer membrane vesicles has been prepared, which can stimulate the secretion of cytokines and may have immunomodulatory effects.

Objective To investigate biomechanical characteristics of femoral neck fracture with different reduction qualities. Methods Three cases of Sawbones artificial femoral models were selected, and two cases of Pauwel III femoral neck fracture were modeled. Three cannulated screws were inserted into the models in the form of inverted triangle to fix the fracture. Two cases maintained different reduction qualities (defined as Model 1 and Model 2). In the 3 third case, no modeling operation was performed (defined as intact model). Then the strain gauges were respectively pasted on regions of interest of the 3 femoral models. Finally, the femur model was applied with the vertical load on mechanical testing machine. Results When the displacement of femoral head reached 4 mm, the average load of intact model, Model 1 and Model 2 was (236.30±5.35), (196.57±3.56), (69.50±2.95) N, showing significant differences. When the displacement of femoral head reached 5 mm, the average load of intact model, Model 1 and Model 2 was (276.7±3.40)，(232.93±2.64)，(80.83±4.54) N, showing significant differences. Conclusions The lower the reduction quality of the femoral neck fracture, the weaker the ability of the femur to bear stress, the higher the probability of nonunion, re-fracture and femoral head necrosis in the process of postoperative rehabilitation.