Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Objective To predict the poorly differentiated subtype of stage T1 invasive lung adenocarcinoma based on the morphological and quantitative characteristics of preoperative CT images.Methods The CT images,clinical information and pathological report of 333 cases with stage T1 lung adenocarcinoma in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and the Second Affiliated Hospital of Naval Medical University were retrospectively analyzed.All data were divided into histological subtypes according to the WHO Classification of Chest Tumors(5th Edition).CT signs include the maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,lobular sign,vacuole sign,air bronchial sign,halo sign,bronchial truncation sign,vascular cluster sign,pleural depression sign.Clinical factors included gender,age,smoking history,tumor markers,and spread through air spaces.Independent predictors of poorly differentiated subtypes of lung adenocarcinoma were obtained via univariate and multivariate logistic regression analysis,and the clinical model,CT model and combined model were constructed based on the analysis results.Results In univariate logistic regression analysis,gender,smoking history,tumor markers,spread through air spaces,maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,vacuole sign and vascular cluster sign were significantly related to poorly differentiated subtypes.Multivariate logistic regression analysis showed that gender,tumor markers,vacuole sign,minimum diameter,and nodule type were independent influencing factors of poorly differentiated subtypes of lung adenocarcinoma.Clinical model,CT model and combined model were constructed based on the analysis results.Area under the curve(AUC)of the clinical model,CT model and combined model were 0.772[95％confidence interval(CI)0.712-0.831],0.776(95％CI 0.714-0.837)and 0.825(95％CI 0.776-0.874)for the poorly differentiated subtypes,respectively.The combined model had a higher AUC,with the better prediction.There was significant difference in predicting lung adenocarcinoma poorly differentiated subtypes between the clinical model and combined model(P=0.019).Conclusion Logistic regression model based on CT signs has good diagnostic value in predicting poorly differentiated lung adenocarcinoma in stage Ⅰ.

Objective To predict the poorly differentiated subtype of stage T1 invasive lung adenocarcinoma based on the morphological and quantitative characteristics of preoperative CT images.Methods The CT images,clinical information and pathological report of 333 cases with stage T1 lung adenocarcinoma in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and the Second Affiliated Hospital of Naval Medical University were retrospectively analyzed.All data were divided into histological subtypes according to the WHO Classification of Chest Tumors(5th Edition).CT signs include the maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,lobular sign,vacuole sign,air bronchial sign,halo sign,bronchial truncation sign,vascular cluster sign,pleural depression sign.Clinical factors included gender,age,smoking history,tumor markers,and spread through air spaces.Independent predictors of poorly differentiated subtypes of lung adenocarcinoma were obtained via univariate and multivariate logistic regression analysis,and the clinical model,CT model and combined model were constructed based on the analysis results.Results In univariate logistic regression analysis,gender,smoking history,tumor markers,spread through air spaces,maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,vacuole sign and vascular cluster sign were significantly related to poorly differentiated subtypes.Multivariate logistic regression analysis showed that gender,tumor markers,vacuole sign,minimum diameter,and nodule type were independent influencing factors of poorly differentiated subtypes of lung adenocarcinoma.Clinical model,CT model and combined model were constructed based on the analysis results.Area under the curve(AUC)of the clinical model,CT model and combined model were 0.772[95％confidence interval(CI)0.712-0.831],0.776(95％CI 0.714-0.837)and 0.825(95％CI 0.776-0.874)for the poorly differentiated subtypes,respectively.The combined model had a higher AUC,with the better prediction.There was significant difference in predicting lung adenocarcinoma poorly differentiated subtypes between the clinical model and combined model(P=0.019).Conclusion Logistic regression model based on CT signs has good diagnostic value in predicting poorly differentiated lung adenocarcinoma in stage Ⅰ.

Objective:To investigate the morphological difference and clinical significance of bilateral lumbar multifidus muscles in patients with unilateral lumbosacral radiculopathy due to lumbar disc herniation and lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on patients with low back pain, lumbar disc herniation and lumbar spondylolisthesis. Patients with lumbar disc herniation or lumbar spondylolisthesis underwent single segment lesion either at L 4, 5 or L 5S 1, while those accompanied with unilateral lumbosacral radiculopathy underwent percutaneous endoscopic lumbar discectomy or conventional open surgery at Qingdao Municipal Hospital between January 2017 and January 2023. Patients with lumbar spondylolisthesis were subdivided into degenerative lumbar spondylolisthesis and isthmic spondylolisthesis. 53 patients with low back pain met the inclusion criteria. 170 patients with lumbar disc herniation met the inclusion criteria, with 101 at L 4, 5 and 69 at L 5S 1 level. 129 patients with lumbar spondylolisthesis met the inclusion criteria, including 91 of degenerative lumbar spondylolisthesis at L 4, 5 level and 9 at L 5S 1 level, and 11 of isthmic spondylolisthesis at L 4, 5 level and 18 at L 5S 1 level. Cross-sectional images at the mid-disc of L 3, 4, L 4, 5 and L 5S 1 segments in MRI were acquired. Relative total cross-sectional area (rTCSA), relative functional cross-sectional area (rFCSA), fat infiltration rate (FIR), relative fat distance (rFD) and differential value FIR (D-FIR) in bilateral lumbar multifidus muscle were measured respectively by using Image J software, and were then used to evaluate the atrophy and fat infiltration of bilateral lumbar multifidus muscles. Results:No significant difference was found between the both sides of multifidus muscle in low back pain patients. L 4, 5 lumbar disc herniation group had smaller rFCSA (0.34±0.10 and 0.35±0.10) and larger FIR [29.92(22.21, 36.46) and 26.48(17.54, 34.55)] and rFD [0.39(0.29, 0.54) and 0.32(0.21, 0.43)] on the affected side compared to the unaffected side in L 4, 5 segment, and had larger FIR (34.83±11.34 and 31.44±10.94) and rFD [0.59(0.43, 0.77) and 0.51(0.37, 0.69)] on the affected side in L 5S 1 segment. L 5S 1 lumbar disc herniation group had smaller rFCSA (0.41±0.11 and 0.42±0.12) and larger FIR [26.84(22.92, 35.29) and 24.02(20.03, 32.87)] and rFD (0.51±0.28 and 0.42±0.26) on the affected side in L 5S 1 segment. L 4, 5 degenerative lumbar spondylolisthesis group had larger FIR (36.49±9.76 and 34.72±9.86) on the affected side in L 4, 5 segment, and had larger FIR [35.03(28.64, 41.85) and 33.34(26.37, 39.76)] on the affected side in L 5S 1 segment. L 5S 1 degenerative lumbar spondylolisthesis group had larger FIR [42.53(37.94, 46.81) and 40.79(30.84, 43.53)] and rFD (1.12±0.79 and 0.94±0.79) on the affected side in L 5S 1 segment. L 4, 5 isthmic spondylolisthesis group had smaller rFCSA [0.24(0.20, 0.30) and 0.29(0.23, 0.34)]and larger FIR [34.19 31.30, 42.39) and 29.43(28.82, 36.89)] and rFD (0.39±0.15 and 0.29±0.15) on the affected side in L 4, 5 segment, and had larger FIR (43.18±12.71 and 34.12±11.63) on the affected side in L 5S 1 segment. L 5S 1 isthmic spondylolisthesis group had larger FIR (40.24±9.34 and 36.37±10.70) on the affected side in L 5S 1 segment. No significant difference was found of the multifidus muscle between the affected and unaffected sides in the proximal adjacent segment of the responsible segment in lumbar disc herniation or lumbar spondylolisthesis group patients. L 4, 5 isthmic spondylolisthesis group had larger D-FIR (6.75±8.46 and 1.78±5.77) in L 4, 5 segment, and had larger D-FIR (9.06±11.59 and 1.54±7.08) in L 5S 1 segment compared to L 4, 5 degenerative lumbar spondylolisthesis group. Grade Ⅱ L 4, 5 lumbar spondylolisthesis group had larger D-FIR (10.73±13.61 and 1.92±7.43) in L 5S 1 segment compared to grade Ⅰ L 4, 5 lumbar spondylolisthesis group. Conclusion:L 4, 5 or L 5S 1 lumbar disc herniation and lumbar spondylolisthesis patients with unilateral lumbosacral radiculopathy had asymmetric atrophy and fat infiltration of multifidus muscle. The atrophy and fat infiltration on the affected side showed greater. The asymmetry appeared in the responsible segment and its distal adjacent lumbar segment. Lumbar spondylolisthesis patients with a lager degree of slip or with isthmic type could be accompanied by more severe asymmetry of multifidus muscle.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

Spinal surgical site infection (SSI), especially deep SSI after internal fixation is difficult in treatment, with long course of disease and poor prognosis. At present, there are many controversies in the diagnosis and treatment of spinal SSI, with unsatisfactory overall efficacy of its diagnosis and treatment. Besides, no diagnosis and treatment guideline based on evidence-based medicine has been in existence. To this end, the Spinal Infection Group of the Orthopedic Branch of the Chinese Medical Doctor Association and the Spinal Infection Group of the Spinal Surgery Branch of the Chinese Rehabilitation Medicine Association jointly organized relevant experts to formulate Evidence-based clinical guideline for the diagnosis and treatment of surgical site infection in spinal trauma ( version 2024) based on an evidence-based approach. A total of 10 recommendations were proposed on the diagnosis and treatment of spinal SSI, so as to provide a clinical reference for the diagnosis and treatment of spinal SSI.

OBJECTIVE: To compare the effectiveness between unilateral biportal endoscopic lumbar interbody fusion (ULIF) and endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) in treatment of lumbar spinal stenosis combined with intervertebral disc herniation. METHODS: A clinical data of 64 patients with lumbar spinal stenosis and intervertebral disc herniation, who were admitted between April 2020 and November 2021 and met the selection criteria, was retrospectively analyzed. Among them, 30 patients were treated with ULIF (ULIF group) and 34 patients with Endo-TLIF (Endo-TLIF group). There was no significant difference in baseline data such as gender, age, disease duration, lesion segment, preoperative visual analogue scale (VAS) score of low back pain and leg pain, Oswestry disability index (ODI), spinal canal area, and intervertebral space height between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stays, and postoperative complications were compared between the two groups, as well as the VAS scores of low back pain and leg pain, ODI, and imaging measurement indicators (spinal canal area, intervertebral bone graft area, intervertebral space height, and degree of intervertebral fusion according to modified Brantigan score). RESULTS: Compared with the Endo-TLIF group, the ULIF group had shorter operation time, but had more intraoperative blood loss and longer hospital stays, with significant differences ( P<0.05). The cerebrospinal fluid leakage occurred in 2 cases of Endo-TLIF group and 1 case of ULIF group, and no other complication occurred. There was no significant difference in the incidence of complications between the two groups ( P>0.05). All patients in the two groups were followed up 12 months. The VAS scores of lower back pain and leg pain and ODI in the two groups significantly improved when compared with those before operation ( P<0.05), and there was no significant difference between different time points after operation ( P>0.05). And there was no significant difference between the two groups at each time point after operation ( P>0.05). Imaging examination showed that there was no significant difference between the two groups in the change of spinal canal area, the change of intervertebral space height, and intervertebral fusion rate at 6 and 12 months ( P>0.05). The intervertebral bone graft area in the ULIF group was significantly larger than that in the Endo-TLIF group ( P<0.05). CONCLUSION For the patients with lumbar spinal stenosis combined with intervertebral disc herniation, ULIF not only achieves similar effectiveness as Endo-TLIF, but also has advantages such as higher decompression efficiency, flexible surgical instrument operation, more thorough intraoperative intervertebral space management, and shorter operation time.
Humans ; Spinal Stenosis/surgery* ; Low Back Pain/surgery* ; Blood Loss, Surgical ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Spinal Fusion

Objective To explore influences of the taper and connecting rib form on supporting performance of the stent, and provide an important scientific basis for structural design and clinical selection of the tapered stent. Methods A nonlinear finite element model for radial support performance of a novel balloon-expandable tapered stent was constructed, and the radial stiffness (RS) and stress distributions of the stent at different tapers (0°, 0.565°and 1.13°) and with different structural forms of stent linker (V-shape, I-shape, C-shape, S-shape, M-shape) were analyzed by plane compression. The relationship between structural design of the vascular stent and its radial support performance was studied. Results The RS of 0°stent, 0.565°stent, 1.13° stent was 2.51, 1.61, 0.85 N/mm, respectively. The RS of 0.565°stent and 1.13° stent was 35.86% and 66.14% lower than that of 0°stent (round straight stent), respectively. Except that the RS of C-shape linker stent was 1.48 N/mm, the RS of I, M, S and V-shape linker stents was not significantly different, which was 2.51, 2.61, 2.41, 2.52 N/mm, respectively, indicating that radial compression resistance of these four linker stents was almost the same. Conclusions Compared with traditional round straight stents, the RS of tapered stents will decrease, and the RS of stents will gradually decrease with the the taper increasing. Among all stent types in this study, except C-shape linker stents, the RS of other linker shapes has little effect on the RS of stents. The radial support performance of the stent can be improved by reducing the taper of the tapered stent, without changing the form of stent connecting ribs.

Objective:To evaluate the volume changes of cervical longus and cervical extensor after anterior cervical discectomy and fusion (ACDF), and the correlation with the clinical efficacy of patients.Methods:All of 57 patients with cervical spondylotic myelopathy who underwent single-segment ACDF surgery from January 2013 to December 2018 were analyzed. The follow-up time was 23.0±4.8 months (range 16-34 months). All included subjects underwent MR examination within 1 week before operation and 3rd, 12th months after operation and at the last follow-up. The axial section cross section area (AxCSA) of the cervical longus and the ratio of length to short diameter line (RLS) at the level of each disc of C 2-C 7 were measured on the axial T2WI. Calculate the volume of the cervical longus based on the layer thickness. At the same time, measure the cervical extensor cross-sectional area (CESA) of the same level including the multifidus, cervical semispinous muscle, semispinous head, splinter head, and cervical splinter muscles, and compare CESA with the corresponding vertebral cross-sectional area (VBA). The ratio is analyzed as the volume of the neck extensor muscle, namely CESA/VBA. At the 3rd and 12th months after operation and at the last follow-up, the axial pain was assessed by visual analogue scale (VAS) for assessing pain, and the modified Japanese Orthopedic Association score (mJOA) and the neck dysfunction index (NDI) were used to assess the functional status of the cervical spine. Analyze the morphological changes of thecervical longus and extensor cervical muscles before and after the operation and during the follow-up period, and analyze the correlation with VAS, mJOA, and NDI. Results:Compared with the preoperative period, the average AxCSA of the surgical segment decreased at the 3rd and 12th months after the operation and at the last follow-up. The difference was statistically significant ( F=24.113, P<0.05), which was changed from 140.84±19.51 mm 2 respectively reduce to 117.74±17.15 mm 2 ( t=6.714, P<0.05), 116.37±18.67 mm 2 ( t=6.841, P<0.05) and 116.27±18.65 mm 2 ( t=6.873, P<0.05). Compared with preoperatively, they were reduced by 16.40%, 17.37% and 17.45%, respectively, while the average RLS of surgical segments increased slightly, and the difference was statistically significant ( F=22.612, P<0.05), which increased from preoperative 1.97±0.67 to 2.73±0.60 (38.58% increased, t=6.380, P<0.05), 2.82±0.64 (43.15% increased, t=6.926, P<0.05) and 2.74±0.62 (39.09% increased, t=6.368, P<0.05). The volume of thecervical longus of the patients decreased after the operation, and the difference was statistically significant ( F=64.511, P<0.05), which decreased from 8853.48±458.65 mm 3 before the operation to 7834.53±461.59 mm 3 (11.51% decreased, t=11.822, P<0.05), 7926.42±456.24 mm 3 (10.47% decreased, t=10.819, P<0.05), 7892.38±450.78 mm 3 (10.86% decreased, t=11.283, P<0.05). There were no statistically significant differences in the non-surgical segment AxCSA, RLS and the volume of thecervical longus at the 3rd and 12th months after surgery and the last follow-up ( P>0.05). There was no statistically significant difference of CESA and CESA/VBA compared to preoperative in the surgical segment and non-surgical segment ( P>0.05). Pearson correlation analysis showed that the volume of cervical longus and VAS at the 3rd month ( r=-0.308, P<0.05), the 12th month ( r=-0.210, P<0.05) and the last follow-up ( r=-0.404, P<0.05) were negatively correlated; Among the volume of cervical longus and NDI in the 3rd month ( r=-0.511, P<0.05), 12th month ( r=-0.518, P<0.05) and the last follow-up ( r=-0.352, P<0.05), there was a negative correlation; However, there was no statistically significant correlation between the cervical longus muscle volume and mJOA at each follow-up time point ( P>0.05); There was no significant correlation between CESA/VBA and VAS, NDI, and mJOA at the 3rd, 12th and last follow-up ( P>0.05). Conclusion:The volume and morphology of cervical longus after ACDF was significantly reduced compared with that before the operation, but the volume and morphology of the cervical extensor muscle did not change significantly. ACDF surgery mainly affects the cervical longus corresponding to the surgical segment, and the volume is negatively correlated with the VAS and NDI during follow-up.

Objective:To investigate the effects of exosomes of human nucleus pulposus cells (NPCs) on the differentiation of urine derived stem cells (USCs) into nucleus pulposus-like cells.Methods:USCs and NPCs were isolated and cultured in vitro. The exosomes of NPCs were extracted and detected by Western-blot. USCs cytoplasm was transfected with GFP lentivirus, while nucleus was transfected with DAPI dye. The NPCs exosomes were transfected with PKH26 dye. After co-incubation for 12 h, USCs and NPCs exosomes were observed by macroscopy. USCs differentiation was induced by NPCs exosomes and non-contact co-culture methods. The relative expression of marker gene mRNA of nucleus pulposus cells in each group and the absorbance at 450 nm wavelength were detected.Results:The isolated USCs had the ability to differentiate into osteocytes, adipocytes and chondrocytes with high expression of marker CD29 (99.57%), CD44 (97.46%) and CD73 (97.71%) and with low expression of negative proteins CD31 (0.59%) and CD45 (0.19%). The isolated NPCs highly expressed nuclear pulposus cell marker COL2A1, ACAN and SOX-9. The exosomes extracted from NPCs showed high expression of exosome marker CD63, CD81 and Tsg101. After 12 h co-incubation, NPCs exosomes fused with USCs membrane and appeared in the cytoplasm of USCs. At 3, 5 and 7 days of co-culture, the absorbance value of USCs cells in exosome group (0.44±0.004, 0.76±0.004, 0.82±0.006) was higher than that in co-culture group (0.39±0.022, 0.63±0.035, 0.69±0.012) ( P<0.05). The mRNA relative expression of USCs nucleus pulposus marker genes ACAN (1.80±0.31, 3.50±0.21, 5.35±0.31, 7.46±0.12), COL2A1 (1.43±0.15, 4.33±0.23, 6.89±0.22, 8.11±0.31), SOX-9 (2.21±0.13, 3.13±0.11, 3.96± 0.14, 4.52±0.26) and HIF-1α (1.45±0.16, 2.14±0.21, 4.31±0.41, 4.01±0.25) in exosomes group were significantly higher than those in the control group ( P<0.05) at the 3rd, 7th, 14th and 21st days. The mRNA relative expression of USCs nucleus pulposus marker genes ACAN (5.69±0.21, 6.69±0.13), COL2A1 (6.33±0.17, 7.89±0.15), SOX-9 (4.19±0.29, 4.38±0.12), HIF-1α (4.49±0.32, 4.96±0.26) in exosomes group were significantly higher than those ACAN (3.69±0.35, 5.13±0.23), COL2A1 (3.40±0.16, 6.79±0.19), SOX-9 (2.26±0.32, 3.69±0.26), HIF-1α (2.39±0.11, 3.96±0.13) in non-contact co-culture group ( P<0.05) at the 14th and 21st days. Conclusion:Human nucleus pulposus exosomes could induce differentiation of human USCs into nucleus pulposus-like cells in vitro. Compared with non-contact co-culture, exosomes have higher induction efficiency and can better maintain the proliferation activity of nucleus pulposus-like cells