Objective:To investigate the effect of different acquisition duration of brain image of 18F-florbetaben(18F-FBB)positron emission tomography(PET)on standardized uptake value(SUV).Methods:Eight subjects who underwent 18F-FBB PET examination in Chinese PLA General Hospital from May 2021 to June 2021 were selected,including 5 persons of healthy control and 3 patients with mild cognitive impairment(MCI).All subjects underwent 18F-FBB PET imaging,and the dynamic PET images of them on brains were continuously acquired for 20 min between 90 and 110 min after the 18F-FBB injection was injected as(3.7-5.5 MBq/kg).Under the situation that other reconstruction parameters did not change,the images were reconstructed at 0-1,0-3,0-5,0-10,0-15 and 0-20 min,respectively.The same of region of interest(ROI)ranges were delineated in bilateral frontal cortex,bilateral temporal cortex,bilateral parietal cortex,posterior cingulate gyrus and cerebellar cortex of each group of images.And then,the corresponding mean standardized uptake value(SUVmean)of each region was obtained.The differences of SUVmean values of different ROI values between each group of data images and the images of 0-20 min were compared and analyzed.Results:There were significant differences in SUVmean between the acquired images in 0-1,0-3,0-5 and 0-10 min and the acquired standard images of 0-20 min(t=-7.569--2.410,P<0.05),respectively.There were no significant differences in SUVmean between the acquired images of 0-15 min and the acquired standard images of 0-20 min in the bilateral frontal lobe,bilateral temporal lobe,bilateral parietal cortex and posterior cingulate gyrus(P>0.05),only there was significant difference in the cerebellar cortex area between them(t=-5.597,P<0.001).Conclusion:The results of 15 min can reach to the similar results of 20 min in acquiring images,which can shorten the time of examination,and enhance the degrees of comfort and cooperation of patients in examination.It has clinical application value.

Objective:To evaluate the potential of 177Lu-prostate specific membrane antigen (PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and compare it with 177Lu-PSMA-I&T. Methods:177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed. Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice. SPECT imaging was performed on 2 patients (60 and 76 years old) with mCRPC from Chinese PLA General Hospital at 24, 72, and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T ((7.40±0.74) GBq). Data were analyzed by using independent-sample t test. Results:177Lu-PSMA-3Q was prepared with the total activity of 74 GBq, the yield rate of 95% (uncorrected), and the radiochemical purity was still above 95% after 168 h at room temperature. The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were (0.75±0.22) and (0.86±0.19) min, and the clearance half-lives were (24.74±3.77) and (29.53±3.42) min. Biodistribution of normal mice showed that the uptake values in the liver, lungs, and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T ( t values: 4.24-8.36, all P<0.05). The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T ((0.856±0.183) vs (0.579±0.126) percentage activity of injection dose per gram of tissue (%ID/g); t=2.78, P=0.024) in 22Rv1 tumor-bearing mice. The rapid clearance pattern resulted in a higher tumor/muscle (T/M) ratio for 177Lu-PSMA-3Q (99.604±11.106), which was significantly higher than that for 177Lu-PSMA-I&T (45.078±10.444; t=7.80, P<0.001). According to SPECT imaging of patients with mCRPC, the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h, with significant difference ( t=7.62, P=0.002). Conclusion:177Lu-PSMA-3Q is easy to label, and has high yield and radiochemical purity, good stability, excellent biological performance, good targeting ability in patients, longer retention time, and fast background clearance rate, which is an ideal prostate cancer treatment drug targeting PSMA.

Objective To investigate the clinical efficacy of bone filling mesh bag combined with pedicle anchoring for the treatment of Stage Ⅲ reducible Kummell disease.Method The 35 paients with Stage Ⅲ reducible Kummell disease were treated with bone filling mesh bag combined with pedicle anchoring from January 2018 to December 2022.The operation Time,intraoperative blood lose,bone cement injection volume and surgical complications were recorded.The VAS score,ODI value,kyphosis Cobb angle and midline height of the injured vertebral were compared at preoperative,postoperative 1 day and last follow-up.Results All patients were followed up for 12-24 months[(15±3.5)months].Operation time was 35-63 min[(45±5.8)min],intraoperative blood loss was 10-35 ml[(20±5)ml],bone cement injection volume was 4.5-7.8 ml[(5.5±1.8)ml].There were 4 cases of bone cement leakage,there were 1 case of intervertebral leakage,2 cases of lateral leakage,1 case of anterior leakage and no patient with intracanal leakage.All bone cement leakage did not lead to clinical symptoms,bone cement poisoning and pulmonary embolism.No cement mass slip.All patients were followed up for 12 to 24 months[(15±3.5)months].VAS scores and Oswestry Disability Index(ODI)values were significantly lower on the first day after surgery than before surgery,with statistical significance(P＜0.05).The 3-month follow-up was slightly higher than that on the first day after surgery,and the difference was not statistically significant(P＞0.05).The midline height and Cobb Angle of the injured vertebra were measured by imaging.The height of the injured vertebra recovered significantly on the first day after operation,and the Cobb Angle decreased significantly,the difference was statistically significant(P＜0.05).The midline height of the injured vertebrae decreased and the Cobb Angle increased slightly at 3 months after the operation,but the difference was not statistically significant(P＞0.05).Conclusion In the the treatment of Stage Ⅲ reducible Kummell disease,Bone filling mesh bag combined with Pedicle anchoring have good clinical efficacy,which can significantly reduce the pain of patients,relieve clinical symptoms,improve spinal function,improve quality of life,and reduce the incidence of bone cement leakage and slippage.

Objective:To compare the clinical utility of 18F-prostate specific membrane antigen (PSMA)-1007 and 18F-FDG PET/CT imaging in newly diagnosed hepatocellular carcinoma (HCC). Methods:From April 2022 to July 2022, 17 patients (14 males, 3 females, age 36-73(54.4±10.1) years) with newly diagnosed HCC who underwent 18F-FDG and 18F-PSMA-1007 PET/CT imaging within 3 d in the First Affiliated Hospital of Zhengzhou University were prospectively enrolled. ROIs were drawn from normal liver tissue (L), abdominal aorta (A), right gluteus medius (M), and SUV max of these regions were compared with the SUV max of primary tumor (T). Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to analyze the data. Results:18F-FDG PT/CT, 18F-PSMA-1007 PET/CT and enhanced MRI detected 1(0, 2), 2(1, 5) and 2(1, 4) tumor lesions of the liver in each patient respectively ( H=7.10, P=0.029), and 18F-PSMA-1007 detected more lesions than 18F-FDG ( P=0.024). Although SUV max of 18F-PSMA-1007 in HCC was significantly higher than that of 18F-FDG (25.7(17.1, 45.1) vs 6.3(2.9, 12.4); z=3.39, P=0.001), there was no significant difference of T/L ratio between 18F-PSMA-1007 and 18F-FDG PET/CT imaging (2.7(2.1, 4.7) vs 1.6(1.0, 4.5); z=0.52, P=0.602). T/A and T/M ratios were significantly higher in 18F-PSMA-1007 PET/CT imaging than those in 18F-FDG PET/CT imaging ( z values: 3.15, 3.53, P values: 0.002, <0.001). 18F-PSMA-1007 PET/CT imaging found high uptake foci in the liver and ribs in 2 cases, which were pathologically confirmed as bone metastasis of HCC, while those lesions were not found by 18F-FDG imaging. Conclusion:Compared with 18F-FDG, 18F-PSMA-1007 PET/CT demonstrates higher tumor uptake, more intrahepatic tumors foci and distant bone metastases.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective:To explore the medical costs and influencing factors of patients diagnosed with Brucellosis in Datong of Shanxi province.Methods:Information on demographics, medical visits, and costs of patients diagnosed with Brucellosis between January 1, 2017, and December 31, 2019, were collected. Health care utilization and medical costs were analyzed from different genders, age groups, underlying diseases, clinical stages, and comorbidities.Results:A total of 2 289 patients (1 715 outpatient and 574 inpatient cases) were included in the analysis. 72.0% (1 649/2 289) were male, with an average age of (49.6±15.5) years; age between 45-59 years was the dominant group (36.2%,829/2 289). The mean age of inpatients (51.4±16.0) was higher than that of outpatients (49.0±15.2)( Z=-4.01, P<0.001). The average number of outpatient visits per outpatient was (1.6±1.5) times. The duration of hospitalization was (14.6±9.9) and (20.8±11.4) days for patients with central nervous system complications and (16.6±9.5) days for vascular system complications. Of the inpatients, 51.0% (293/574) had underlying diseases, and 30.3% (174/574) had endocrine and metabolic diseases. 54.0% (310/574) of inpatients were diagnosed with acute Brucellosis, and 46.0% (264/574) were diagnosed with chronic Brucellosis. A total of 64.3% (369/574) of inpatients had complications, 30.3% (174/574) of digestive system complications, followed by skeletal system complications (29.1%, 167/574). Among outpatients, age significantly affected medical costs ( P<0.001). For inpatients, age and complications and treatment effect were influential factors ( P<0.05). Patients with the combined skeletal system and central nervous system complications had significantly higher medical costs ( P<0.001). Conclusions:The medical costs for outpatient cases of Brucellosis were moderate. However, the economic burden was higher for inpatients, especially those with skeletal and neurological complications. Early detection, diagnosis, and treatment of cases were essential to avoid chronic Brucellosis and its complications and reduce medical costs.

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Animals ; Bone Regeneration ; Indoles ; Nanoparticles ; Osteogenesis ; Pharmaceutical Preparations ; Polymers ; Rats

In order to avoid the intra- and post-operative risks caused by massive blood loss, there are various clinical methods for evaluating the blood supply of the tumor and the distribution of blood vessels around the tumor before surgery, such as dynamic enhanced CT, dynamic enhanced magnetic resonance imaging, digital subtraction angiography, etc. And there are a variety of pre- and intra-operative methods to reduce tumor bleeding, such as transarterial vertebral tumor embolization, percutaneous or transpedicular injection of Onyx/NBCA, antifibrinolytic drugs, controlled deliberate hypotension, etc. This article reviews on spinal tumor blood supply assessment and the methods to reduce the amount of surgical bleeding.

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.
Animals ; Colitis, Ulcerative/microbiology* ; Mice ; Mice, Inbred C57BL ; Porphyromonas gingivalis/pathogenicity* ; Protein-Arginine Deiminases ; Virulence Factors

Objective:To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded by graphene oxide (GO) on cartilage repair in two KOA animal models.Methods:30 male New Zealand rabbits aged 12 weeks were randomly divided into A group ( n=15) and B group ( n=15). In the A group, the KOA model was established by the improved Hulth and cartilage defect method, and in the B group, the KOA model was established by the modified papain controlled-release injection method. After the modeling, the rabbits model in each group were divided into 4 subgroups, including blank control group ( n=3), GO group ( n=4), UCMSCs group ( n=4) and GO+UCMSCs group ( n=4). In these subgroups, the rabbit models were respectively treated injected with 0.5 ml of NaCl solution with 9 g/L, GO granular lubricant (GO with 30 μg/ml and solvent with hyaluronic acid with 0.25%), UCMSCs suspension (5×10 6 /ml), and mixed suspension of UCMSCs loaded by GO (GO with 30 μg/ml and UCMSCs with 5×10 6/ml) in right knee joint cavity. The serum levels of NO, collagen type Ⅱ(COL-Ⅱ), glycosaminoglycan (GAG), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Results:Eight weeks after the treatment, the serum levels of NO, IL-6 and TNF-α in GO+UCMSCs group were lower than those of the blank control group (all P<0.01), and the serum levels of COL-Ⅱ and GAG in GO+UCMSCs group were higher than those of the blank control group (all P<0.01). The serum NO level of the blank control group in group A was lower than that of the blank control group in group B [(22.097±0.352) ng/ml vs (23.662±0.056) ng/ml, P<0.05]. The serum COL-Ⅱ levels of the UCMSCs group and GO+UCMSCs group in group A were higher than those of group B respectively [(15.589±0.063) ng/ml vs (14.429±0.092) ng/ml, and (19.372±0.063) ng/ml vs (16.257±0.416) ng/ml, all P<0.01]. The serum GAG levels of the blank control group and the GO+UCMSCs group in group A were higher than those in group B respectively [(23.832±0.891) ng/ml vs (18.709±0.552) ng/ml, and (37.439±2.155) ng/ml vs (26.554±0.450) ng/ml, all P<0.01). The serum IL-6 levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(16.082±0.323) ng/ml vs (18.367±0.861) ng/ml, P<0.05; (7.426±0.294) ng/ml vs (8.680±0.242) ng/ml, P<0.01]. The serum TNF-α levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(9.466±0.177) ng/ml vs (10.013±0.197) ng/ml, P<0.05; (5.139±0.183) ng/ml vs (6.210±0.058) ng/ml, P<0.01]. Conclusions:GO loaded UCMSCs can promote the secretion of chondrocytes in rabbit KOA models, reduce inflammatory levels in joints, and play a role in cartilage repair.