Objective To investigate the effects and feasibility of mini-thoracotomy focus cleaning in the management of cavitary pulmonary tuberculosis or pulmonary tuberculoma. Methods The mini-thoracotomy approach was adopted in patients with cavitary pulmonary tuberculosis or pulmonary tuberculoma who had undergone long-term anti-tuberculosis therapy or needed a re-treatment.Eight patients with chronic fibro-cavitative pulmonary tuberculosis and 10 patients with pulmonary tuberculoma underwent focus cleaning, irrigation, and folding suture. Results All the 18 patients were cured clinically, with their sputum findings turning negative for bacteria and pulmonary shadows subsiding. No operative complications occurred. Follow-up for 1～4 years found no recurrence. Conclusions Focus cleaning is an effective surgical alternative for pulmonary tuberculosis after proper selection of cases. The procedure is minimally invasive and patient's pulmonary function can be protected to the greatest possible advantage.

Objective To study clinical features of severe craniocerebral injuries complicated by upper cervical vertebral injuries so as to have a deeper understanding and higher vigilantness. Methods Twenty-nine cases of severe craniocerebral injuries complicated by upper cervical vertebral injuries were clinically analyzed. Results Injury causes included traffic accident in 26 cases, fall in one, rolling down in one and mine collapse in one. Treatment results showed that 16 cases survived and 13 died. As for Glasgow Outcome Scale (GOS) score, two cases were ranked at grade Ⅴ, seven at grade Ⅳ, six at grade Ⅲ, one at grade Ⅱ and 13 at grade Ⅰ. Conclusions The severe craniocerebral injuries complicated by upper cervical vertebral injuries are critical and complex mainly because the severe craniocerebral injuries can be paid more attention and diagnosed and treated early while the upper cervical vertebral injuries are easy to be neglected, as gives rise to missed injuries, lack of timely management and high mortality. Therefore, various severe complications are liable for deaths.

After analyzing the correlation coefficient (r) of mid-clavicular liver size (MCL) and mid-sternal liver size (MSL), and the rate of correspond once between palpation and B Ultrasound of spleen, it was found that the "r" of MCL and MSL is 0. 6476 and 0. 5623 respectively, the correspond once rate of spleen is 76. 23%, This result shows that the examiner must master the palpation technique well and B Ultrasound should be used in the screening of schistosomiasis japonica if possible.

Objective:To synthesize Gd labeled probe targeting transporter protein(TSPO) 2-(8-amino-2-(4-chlorophenyl)imidazo[1, 2-a]pyridine-3-yl)- N, N-dipropylacetamide (CB86)-diethylene triamine pentaacetic acid (DTPA), and investigate its MRI effect in rheumatoid arthritis (RA) model. Methods:CB86-DTPA was prepared by coupling a bifunctional chelating agent, and then chelated with Gd to obtain MRI targeted contrast agent CB86-DTPA-Gd. The cytotoxicity, MR relaxation rate and in vitro stability of CB86-DTPA-Gd were determined. RA model was established with Freund′s adjuvant and the biodistribution study and MRI was performed. The RA lesion and its surrounding normal tissue were used as regions of interest (ROI) to calculate the signal to noise ratio (SNR). Independent-sample t test was used to analyze the data. Results:CB86-DTPA-Gd had excellent biosafety and a good MR relaxation rate ( r1=11.05 mmol·L -1·s -1). The survival rate of RAW264.7 cells and 4T1 cells was still more than 90% at the maximum concentration (20 μmol/L) of Gd 3+. CB86-DTPA-Gd also exhibited good stability in human serum and phosphate buffer saline solution (PBS; pH=7.4). The in vivo biodistribution showed that CB86-DTPA-Gd had better inflammatory targeting efficiency, and the uptake of Gd in the inflamed site of the ankle joint was still (2.33±0.29) percent dose rate per gram of tissue (%ID/g) at 120 min after injection. MicroMRI showed that the inflammation of the right ankle joint displayed significant enhancement after the injection of CB86-DTPA-Gd and Gd-DTPA. The SNR of CB86-DTPA-Gd group was up to 23.21±1.44, and the maximum intensification time was 90 min after injection, and can be significantly inhibited by CB86-DTPA at all time points ( t values: 6.083-12.451, all P<0.05), while the Gd-DTPA group had a strengthening time of 30 min after injection with the SNR of 16.12±1.24. Conclusion:CB86-DTPA-Gd shows good macrophage targeting and good uptake in arthritic reaction sites, and is expected to be a novel MRI molecular probe for peripheral inflammation imaging.

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Objective:To evaluate the clinical value of combined detection of placenta associated 8 (PLAC8) and platelet activating factor acetylhydrolase (PLA2G7) for early identification of sepsis and non-infectious systemic inflammatory response syndrome (SIRS).Methods:A cross-sectional study was conducted. A total of 189 febrile patients suspected infection who were admitted to Huashan Hospital, Fudan University from October 2022 to April 2023 were included. Based on etiological, laboratory test results and clinical data, patients were classified as infection or non-infection, and further classified as sepsis or non-infectious SIRS according to diagnostic criteria. Real-time fluorescence polymerase chain reaction was used to detect the mRNA levels of PLAC8 and PLA2G7 in peripheral venous blood of patients. Hematology, inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin, sepsis-related organ failure assessment (SOFA) score, and the difference of cycle threshold (Ct) values between PLA2G7 and PLAC8 ((PLA2G7-PLAC8)ΔCt value))were compared between the sepsis and non-infectious SIRS groups. Statistical comparison was analyzed using Mann-Whitney U test, and the diagnostic performance of (PLA2G7-PLAC8)ΔCt value in discriminating sepsis from non-infectious SIRS was evaluated using receiver operating characteristic curve. Results:Among the 189 febrile patients suspected infection, there were 80 non-infectious patients, including 51 non-infectious SIRS patients, and 109 infection patients, including 53 sepsis patients. The neutrophil ratio, CRP, IL-6, procalcitonin, and SOFA score of non-infectious SIRS patients were lower than those of the sepsis group, and the differences were all statistically significant ( Z=-2.70, -3.11, -2.16, -3.76 and -2.33, respectively, all P<0.05). The (PLA2G7-PLAC8)ΔCt value in the non-infectious SIRS group was 4.38(1.41), which was lower than 8.18 (6.19) in the sepsis group, with a statistically significant difference ( U=193.50, P<0.001). The area under the receiver operating characteristic curve (AUROC) for (PLA2G7-PLAC8)ΔCt value in the differential diagnosis of sepsis and non-infectious SIRS was 0.859, with the optimal cut-off value of 5.86. The sensitivity and specificity were 82.2% and 71.9%, respectively. When combined with procalcitonin, the AUROC was 0.917, with a sensitivity of 95.6% and specificity of 70.6%. Conclusions:The (PLA2G7-PLAC8)ΔCt value in peripheral blood has good clinical value for early identification of sepsis and non-infectious SIRS, especially when combined with procalcitonin, which could further improve the accuracy of differential diagnosis.

ObjectiveTo investigate the expression and clinical significance of serum exosomal microRNA(miRNA)-221-3p in hepatocellular carcinoma (HCC). MethodsA total of 66 patients who underwent surgery in Nanjing Drum Tower Hospital, Nanjing University Medical School, from February 2010 to December 2014 and were diagnosed with HCC were enrolled as HCC group, and 25 individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group. The exosome extraction kit was used to isolate the exosomes in serum; Western blotting was used to measure the expression of exosome markers; a transmission electron microscope was used to observe the morphology of serum exosomes; quantitative real-time PCR was used to measure the expression of serum exosomal miRNA-221-3p. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method and the log-rank test were used to analyze the association of the expression of serum exosomal miRNA-221-3p with prognosis, and the Cox proportional hazards regression model was used to analyze the influencing factors for prognosis. ResultsSerum exosomes were small membranous vesicles with a diameter of about 40-100 nm, and HSP70, Alix, and CD63 were expressed in the exosomes. The HCC group had significantly higher expression of serum exosomal miRNA-221-3p than the control group (U=354.00, P＜0.001). In the patients with HCC, the high expression of serum exosomal miRNA-221-3p was associated with tumor size (χ2=6.016, P=0.014), capsular invasion (χ2=7.580, P=0.006), and TNM stage (χ2=6.340, P=0012). In addition, the HCC patients with high expression of serum exosomal miRNA-221-3p had a significantly lower overall survival rate than those with low expression (χ2=17.105, P＜0.001). The multivariate analysis showed that the expression of serum exosomal miRNA-221-3p (hazard ratio ［HR］=2.434, 95% confidence interval ［CI］: 1.178-5.027, P=0.016) and tumor stage (HR=2.653, 95% CI: 1.222-5.760, P=0.014) were independent risk factors for the prognosis of patients with HCC. ConclusionThere is a significant increase in the expression of serum exosomal miRNA-221-3p in HCC patients, which provides a reference for the diagnosis and prognostic evaluation of HCC.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Objective To synthesize a novel 18 F labeled probe targeting translocator protein ( TSPO) ligand 2-( 5, 7-diethyl-2-( 4-( 2-fluoroethoxy ) phenyl ) pyrazolo [ 1, 5-a ] pyrimidin-3-yl )-N, N-diethylacet-amide (VUIIS1008), and evaluate its biodistribution and imaging in rheumatoid arthritis (RA) model. Methods The tosylate substrate was labeled with 18 F using a tosyloxy for fluorine nucleophilic aliphatic substitution to obtain 18 F-VUIIS1008. The labeling efficiency, radiochemical purity, and stability in vitro were determined. In vitro cellular uptake and competitive binding assay were performed on RAW264.7 mac-rophage cells. Biodistribution and microPET/CT imaging were investigated on RA mice established by Com-plete Freund's Adjuvant. Two-sample t test was used to analyze the data. Results 18 F-VUIIS1008 was syn-thesized with the labeling yield up to (41.00±5.00)％, the radiochemical purity>98.00％, and the specific radioactivity >1. 52 × 108 MBq/mmol. 18 F-VUIIS1008 was highly stable with the radiochemical purity >98. 00％ at 4 h after incubation in mouse serum. In vitro, it also exhibited high specific TSPO binding in RAW264.7 macrophage cells. The uptake ratio was (14.00±0.30)％ at 1 h after incubation, and decreased significantly ((4.00±0.70)％;t=12.894, P<0.05) after adding excessive unlabeled VUIIS1008. The half maximal inhibitory concentration (IC50) of 18F-VUIIS1008 binding to TSPO was 0.05 nmol/L in RAW264.7 macrophage cells. In vivo distribution results showed that the uptake of 18 F-VUIIS1008 in the left arthritic ankles reached the peak value of (1.33±0.02) percentage activity of injection dose per gram of tissue (％ID/g) at 1 h after injection. The radioactivity ratio of left ankle arthritic tissue to blood ( A/B) and to normal muscle ( A/M) was 4.40±0.22 and 1.65±0.07 respectively. MicroPET/CT imaging demonstrated that 18F-VUIIS1008 could specifically target and retained in the inflammation site. Conclusion 18 F-VUIIS1008 can be easily synthe-sized with high radiochemical purity and can clearly visualized in RA imaging with low background, suggesting its potential as a novel promising molecular probe targeting TSPO for RA PET imaging.