Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.

PURPOSE: End-stage knee osteoarthritis (OA) patients are the primary candidates for total knee arthroplasty (TKA). However, most morphological refinements of TKA prosthesis are based on anatomical data from the knees of healthy individuals. This study aimed to determine whether differences exist in key bony morphological characteristics of the distal femur and proximal tibia between osteoarthritic knees and healthy knees. METHODS: This was a retrospective cross-sectional observational study with a case-control design. Patients who were aged ≥ 50 years, had no history of trauma, fracture, or surgery in the studied knee, and had no obvious knee flexion contracture were included in this study by CT scans. Patients who met the American College of Rheumatology clinical criteria for knee OA were included in the study group. Kellgren-Lawrence grade III or IV knees were studied (for bilateral cases, the more severely affected knee was chosen). Patients who presented with unilateral knee pain or trauma were included in the control group, with CT scans from the opposite (asymptomatic) knee used for analyzing. The studied knee had a Kellgren-Lawrence grade of 0 or I and showed no abnormalities upon physical examination. Archived knee CT scans from 160 patients were divided into 2 groups: the study group (80 moderate-to-severe OA knees) and the control group (80 healthy knees). After 3-dimensional reconstruction and virtual cutting using a CT workstation, 13 morphological parameters of the distal femur and proximal tibia were compared between the 2 groups using independent-samples t-tests. RESULTS: No significant group differences in the femoral anteroposterior dimension (p = 0.797), height of the lateral femoral condyle (p = 0.268), posterior condylar angle (p = 0.240), tibial anteroposterior dimension (p = 0.536), or tibial lateral anteroposterior dimension (p = 0.702) were observed. However, the femoral mediolateral dimension (p = 0.002), distal femoral aspect ratio (femoral mediolateral dimension/femoral anteroposterior dimension) (p < 0.001), height of the femoral trochlear groove (p < 0.001), height of the medial femoral condyle (p < 0.001), tibial mediolateral dimension (p = 0.001), proximal tibial aspect ratio (tibial mediolateral dimension/tibial anteroposterior dimension) (p = 0.004), tibial medial anteroposterior dimension (p = 0.005), and tibial asymmetry ratio (tibial medial anteroposterior dimension/tibial lateral anteroposterior dimension) (p = 0.006) were all significantly greater in the study group. CONCLUSION Knees with moderate-to-severe OA are significantly wider than healthy knees, and OA is a risk factor for increased tibial platform asymmetry. When refining the morphological parameters of TKA prostheses, the specific bony morphological characteristics of OA knees should be taken into account to reduce the potential risk of femoral or tibial component underhang and facilitate optimal balance between tibial component fit and rotational alignment.
Humans ; Osteoarthritis, Knee/pathology* ; Male ; Female ; Cross-Sectional Studies ; Retrospective Studies ; Arthroplasty, Replacement, Knee ; Middle Aged ; Aged ; Case-Control Studies ; Prosthesis Design ; Knee Prosthesis ; Femur/anatomy & histology* ; Tibia/anatomy & histology* ; Tomography, X-Ray Computed ; Knee Joint/diagnostic imaging*

Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.

By analysing the similarity between defense qi and leukocytes in terms of function， site of action， and circadian rhythm， it is proposed that in traditional Chinese medicine （TCM）， the pathogenesis of leukopenia is defense qi deficiency. By analyzing the relevant discussions on the generation and transmission of defense qi in TCM classics， it is believed that the original qi in lower jiao （焦） is the source of defense qi， while the water and grain qi in middle jiao enriches defense qi， and the upper jiao transmits and distributes defense qi to the whole body. Therefore， when treating leukopenia after chemotherapy with TCM， Guilu Erxian Gelatin （龟鹿二仙胶） and Yougui Pill （右归丸） are often used to tonify the kidney and supplement essence， and moxibustion at Guanyuan （CV 4） and Qihai （CV 6） is usually accompanied to replenish the original qi in lower jiao and enrich the source of defense qi. Guipi Decoction （归脾汤）， Buzhong Yiqi Decoction （补中益气汤）， Shenling Baizhu Powder （参苓白术散）， and Sijunzi Decoction （四君子汤） are often suggested to strengthen spleen and replenish qi， in combination with moxibustion at Zhongwan （CV 12） and Zusanli （ST 36） to transport the spleen and stomach in the middle jiao to enrich the defense qi. Modified Guizhi Decoction （桂枝汤） to harmonize nutrient and defensive aspects is often used， and moxibustion at Dazhui （GV 14） and Feishu （BL 13） or scraping is added to dredge the striae and interstice in the upper jiao and promote transmission and dissemination of the defense qi. Considering the whole process of generation and distribution of defense qi， it is suggested to choose the most appropriate treatment modality flexibly， and combine internal treatment with external treatment， in order to provide ideas for the treatment of leukopenia in tumour patients.

Objective:To evaluate the safety and efficacy of the technique of minimally invasive separation surgery with small incision and free hand screw placement in patients with spinal metastases.Methods:Retrospectively reviewed the clinical data of 49 consecutive patients from May 2019 to December 2019 who underwent minimally invasive separation surgery with small incision and free hand screw placement for metastatic spinal tumors. Among them, there were 21 males with an average age of 55.62±2.97 years (range: 26-75 years) and 28 females with an average age of 52.50±1.76 years (range: 34-72 years). For patients who have primary tumor history with multiple metastases, routine pre-operative biopsy is not required; but for patients whose primary tumor is unknown and who have no history of tumor, pre-operative biopsy diagnosis is required. Before operation, Karnofsky Performance status (KPS) scoring system was used to evaluate the general condition of patients, Spinal Instability Neoplastic Score (SINS) scoring system was used to evaluate the spine stability, epidural spinal cord compression (ESCC) grading system was performed to access the degree of spinal cord nerve compression, and Frankel grading system was used to evaluate the neurological function. For patients who meet inclusion and exclusion criteria ware performed for decompression and internal fixation by a minimally invasive separation surgery with small incision and free hand screw placement. The demographic, neurological function, complications and perioperative data were collected and analyzed, including pre-operation neurological function, operation time, intraoperative blood loss, postoperative suction drainage, drainage tube extraction time, complications rates, hospital stay, and assessment of neurological recovery at 4 weeks after surgery.Results:Preoperative coil embolization was performed in 1 patient with kidney cancer. The mean intraoperative blood loss was 748.60±79.39 ml. Comparison of intraoperative blood loss of 12 rich blood supply (liver cancer, kidney cancer, thyroid cancer) and 37 poor blood supply spine metastases (970.80 ml vs 676.50 ml) was not statistically significant ( P>0.05). The average operation time was 213.40±9.87 min. The operation involved 1 segment was performed in 41 patients (83.67%) and 8 patients had separation of 2 or more segments. The post-operative drainage before discharge was 494.02±63.30 ml. The average drainage tube retention time was 4.50±0.26 d and the average length of hospital stay was 7.35±0.38 d. The post-operative hospitalization was 5.31±0.29 d. 79.59% of patients had the neurological functions of Frankel grade C and D before surgery and 95.92% of patients exhibited stable and improved function at 4 weeks after surgery which was significantly improved comparing with that before surgery ( P<0.05). The complications occurred were dural rupture (1 case), infection (1 case) and hematoma (1 case). Comparison:The minimally invasive separation surgery with small incision and free hand screw placement could achieve less trauma, low complications rate, rapid postoperative recovery. It is also comparable to the traditional open separation surgery in terms of spinal stability and improvement of neurological functions. It is an excellent alternative for patient with spinal metastases.

Objective To investigate the level of plasma MALAT1 in breast cancer(BC)patients and its clinical significance.Methods The expression levels of MALAT1 different fragments were detected in plasma from 10 healthy controls.The expressions of GAPDH and MALAT1 of plasma samples collected from 102 preoperative breast cancer patients,64 postoperative breast cancer patients,47 breast benign tumor patients and 50 healthy controls were determined by RT-qPCR.The potential association between plasma GAPDH level and cases′clinicopathologic features was analyzed to evaluate the stability of GAPDH. Receiver operating characteristic(ROC)curve was constructed to evaluate the diagnostic efficiency of MALAT1,CA153 and CEA for breast cancer.Meanwhile, the association between MALAT1 level and the clinicopathologic features and the expressions of MALAT 1 between preoperative and postoperative BC patients were analyzed.T-test and one-factor ANOVA test were used for normal distribution of quantitative data.The rank sum test was used for non-normal distribution of data.Results GAPDH level was stable in female plasma and was not affected by age and pathology(P>0.05).GAPDH can be used as a reference for plasma lncRNA detection.The levels of different MALAT1 fragments were inconsistent(χ2=27.042,P<0.001).Levels of MALAT1 were significantly elevated in preoperative BC patients[5.58(2.17-12.34)] compared with breast benign tumor patients and healthy controls[1.08(0.61 -2.58)(Z=6.209,P<0.001),1.63(0.98 -3.51)(Z=4.871,P<0.001)].However, there was no significantly difference between breast benign tumor patients and healthy controls(Z=-1.675,P=0.094).The MALAT1 levels of low grade patients(gradeI and II)were higher than those of breast benign tumor patients(Z=5.593,P<0.001).The relative expression of MALAT1 in postoperative plasma was significantly reduced(Z=-2.248,P=0.025).Areas under the ROC curve of MALAT1,CA153 and CEA were 0.744,0.619 and 0.553 respectively.The sensitivity and specificity were 54.1%,60.0%,70.0% and 86.3%,66.7%, 44.1%respectively.The levels of MALAT1 were associated with TNM stage(Z=-1.982,P=0.047), lymph node metastasis(Z=-2.186,P=0.029)and tumor differentiation(Z=-2.435,P=0.015). Conclusion The expressions of MALAT1 were highly elevated in BC patients.Plasma MALAT1 may be an important biomarker for the diagnosis of breast cancer.

Some of the patients with rectal cancer are less sensitive to preoperative concurrent chemoradiotherapy (CCRT).Patients who are resistant to CCRT have a poor local tumor control and CCRT may also increase adverse reactions.The sensitivity of rectal cancer patients to CCRT can be predicted by magnetic resonance imaging (MRI),positron emission tomography,serum carcinoembryonic antigen,molecular biomarkers and gene expression profiling before treatment.According to the predicted results,the clinicians are instructed to choose individualized treatment for the patients so that the therapeutic effects of rectal cancer are further improved.

Objective To explore the effects of improvements on setup error ( SE ) and clinical target ( CTV ) margin of supraclavicular field ( SCF ) by using moisture-cured resin cushion and breast bracket for lower neck fixation in breast cancer patients who underwent post-mastectomy radiotherapy. Methods Totally 13 patients with breast cancer who underwent post-mastectomy radiotherapy were enrolled. All patients were immobilized by breast bracket and moisture-cured resin cushion. Firstly, each patient′s lower neck and head was fixed well by moisture-cured resin cushion, filling the gap between the neck and breast bracket. Secondly,each patient underwent the cone-beam CT ( CBCT) at the first, tenth and twentieth treatment after positioning. Then these CBCT images were registered to the planning CT to determine setup errors in translational and rotational directions, and SCF CTV margins by the systematic and random errors were evaluated. Results The setup errors in x (left-right), y (superior-inferior), z (anterior-posterior) translational directions were (2. 16 ± 1. 25), (1. 50 ± 1. 28), (1. 94 ± 1. 12) mm and (1. 76 ±1. 87)°, (1. 82 ±1. 12)°, (0. 99 ±0. 58)°, respectively in θ (pitch degree),Ф(roll degree),ψ( yaw degree) rotational directions. Non-parametric rank test ( Mann-Whitney U test) was performed with previous data, the differences of the setup error in y, z,θ directions were statistically significant ( Z =4. 152, 3. 415, 2. 053, P<0. 05). The margins from CTV were 4. 07, 4. 03 and 3. 73 mm in x, y and z directions, respectively. Compared with the previous study on SCF, CTV margin required 8, 8 and 6 mm in x, y and z axis directions, the volume of CTV to PTV were decreased by 32. 73% on average. Conclusions Compared with plastic circular pillow alone, moisture-cured resin cushion with breast bracket locating method could reduce setup errors in SCF target region. The margins from CTV to PTV weredecreased to 4. 07, 4. 03 and 3. 73 mm in x, y and z axis directions at least.

Objective To detect serum ubiquitin-like with PHD and ring finger domains 1 (UHRF1) levels in the patients with esophageal squamous cell carcinoma (ESCC),and analyze their differences among different clinicopathological features subgroups and changes during the perioperative period.Methods Serum samples from 130 preoperative ESCC patients,62 patients 1 week after operation,14 patients 1 week and 2 weeks after operation and 67 healthy controls,and clinicopathological data from ESCC patients were collected.Serum UHRF1 levels were detected by ELISA,and the differences among different groups were analyzed with independent t test,paired t test or one-way ANOVA.Results Serum UHRF1 levels in 130 preoperative ESCC patients were significantly higher than that in healthy controls (t =7.680,P ＜ 0.01),and they were related to the ESCC patients' tumor size,differentiation degree,tumor invasion,lymph nodes metastasis and pTNM stage (P ＜ 0.05),but unrelated to the patients' age,gender,tumor location and types (P ＞ 0.05).Serum UHRF1 levels in 62 postoperative patients were significantly lower than that before operation (t =5.530,P ＜ 0.01),but similar to that in healthy controls (t =1.622,P ＞ 0.05).The serum UHRF1 levels before operation,1 week after operation and 2 weeks after operation in 14 ESCC patients decreased gradually (F =7.595,P ＜ 0.01).Conclusion Serum UHRF1 levels may be a potential biomarker for dynamically monitoring perioperative ESCC patients.

Objective To study the expression of macrophage inflammatory protein-1α(MIP-1α),inter-feron gamma inducible protein 10(IP -10)and angiopoietin -1 (Ang -1)in primary acute myelogenous leukemia (AML),and clarify their clinical significance.Methods ELISA was used to detect the expressions of MIP -1α,IP-10 and Ang -1 in serum samples from 54 AML patients(observation group),and twenty volunteers(normal control group).Results The expression levels of MIP -1α,IP -10 and Ang -1 in the observation group[(198.813 ± 53.923)pg/mL,(2.332 ±0.745)ng/mL,(1.593 ±0.447)ng/mL]were significantly higher than the normal control group[(153.309 ±44.475)pg/mL,(1.569 ±0.485)ng/mL,(0.838 ±0.333)ng/mL](t =3.369,5.133,6.856, all P <0.05).Subgroup analysis,during the groups of better -risk,intermediate -risk and poor -risk,the contents of MIP -1αwere (141.524 ±27.510)pg/mL,(196.370 ±31.966)pg/mL,(269.892 ±54.795)pg/mL;the contents of IP -10 were (2.085 ±0.332)ng/mL,(2.307 ±0.696)ng/mL,(2.685 ±0.348)ng/mL;the contents of Ang -1 were (1.248 ±0.454)ng/mL,(1.599 ±0.386)ng/mL,(1.951 ±0.359)ng/mL.The levels of MIP -1αand Ang -1 in the better -risk group were significantly lower than those in the intermediate -risk group and poor -risk group (q =6.100,11.438,3.603,5.742,all P <0.05).While the levels of IP -10 had no closely correlation with NCCN risk status(q =1.225,2.643,2.016,all P >0.05).There were remarkable correlation between the serum expression levels of MIP -1αand Ang -1 (r =0.324,P <0.05).Conclusion There are differences of serum MIP -1α, IP -10 and Ang -1 in the different NCCN prognosis groups,which reflect they may have certain guiding significance in the choice of clinical treatment and the prognosis for newly diagnosed AML.