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Yanghui Jin,1 Shengping Hu,1 Junkai Feng,2 Jianjun Ni3 1Department of Orthopaedics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Pharmacy, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jianjun Ni, Department of Pharmacy, Department of Orthopaedics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email njj19700912@163.comPurpose: To evaluate the accuracy of metagenomic next-generation sequencing (mNGS) for rapid diagnosis of spinal tuberculosis using spinal tissue specimens.Methods: Medical data regarding suspected spinal tuberculosis were retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of mNGS were calculated to determine its diagnostic efficacy, and these values were compared with culture and composite reference standard (CRS).Results: Two hundred and three cases of spinal tuberculosis were included for analysis. The sensitivity, specificity, PPV, NPV, and AUC of mNGS compared with culture were all very good. When CRS was used for the comparison, the sensitivity of mNGS and culture were 71.2% and 73.0%; the specificity and PPV were 100% in all cases; the NPV were 74.2% and 75.4%; the AUCs were all 0.86. The sensitivity and NPV of culture were slightly higher than that of mNGS; however, the diagnostic efficacy of mNGS and culture was consistent (P > 0.05).Conclusion: Spinal tissue specimens for mNGS testing had very good accuracy for diagnosing spinal tuberculosis.Keywords: spinal tuberculosis, culture, mNGS, molecular test, diagnostic accuracy

This study aimed to compare the clinical efficacy of nano-hydroxyapatite/polyamide 66 strut （n-HA/PA66 group） with autogenous iliac bone grafts（AIBG group） in anterior reconstructive surgery for lumbar spinal tuberculosis（LSTB）. A total of 67 patients with LSTB who underwent one-stage combined anterior-posterior surgery using an n-HA/PA66 strut or an autogenous iliac bone graft were studied retrospectively at a mean follow-up of 33.8±7.0 months. The Data about erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Orthopaedic Association (JOA) and Oswestry Disability Index (ODI)score, visual analog scale (VAS) score, American Spinal Injury Association（ASIA ）grade, and Cobb's angle were recorded and compared between the two groups before surgery, three months after surgery and at the last follow-up. At the last follow-up, both groups achieved satisfactory bony fusion without recurrence of tuberculosis, while ESR, CRP, VAS, ASIA grade, and Cobb angle were significantly improved at the last follow-up compared to the preoperative. The n-HA/PA66 group was superior in operation time(P

OBJECTIVE: To investigate the safety of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bioactive support in bone grafting and fusion for elderly patients with lumbar tuberculosis, and to analyze its effectiveness and advantages by comparing with autologous iliac bone grafting. METHODS: A retrospective analysis was performed on 48 elderly patients with lumbar tuberculosis who met the selection criteria between January 2017 and January 2020. The patients all underwent one-stage posterior pedicle screw internal fixation combined with anterior lesion removal and bone grafting and fusion, of which 23 cases applied n-HA/PA66 bioactive support+allogeneic bone graft (n-HA/PA66 group) and 25 cases applied autologous iliac bone graft (autologous iliac bone group). There was no significant difference between the two groups in gender, age, bone density, disease duration, lesion segment, and preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Cobb angle (P>0.05). The operation time, intraoperative blood loss, and postoperative complications, as well as the VAS score, JOA score, American Spinal Injury Association (ASIA) spinal cord injury grading, Cobb angle, and bone fusion were recorded and compared between the two groups. RESULTS: The operations were completed successfully in both groups. n-HA/PA66 group had significantly less operation time and intraoperative blood loss than the autologous iliac bone group (P0.05). Postoperative complications occurred in 3 cases (13%) in the n-HA/PA66 group and 10 cases (40%) in the autologous iliac group, and the difference in the incidence of complications between the two groups was significant (χ(2)=4.408, P=0.036). The postoperative VAS scores and JOA scores significantly improved when compared with the preoperative scores in both groups (P0.05) at the other time points. At last follow-up, according to the ASIA grading, the effective improvement rate was 86% (18/21) in the n-HA/PA66 group and 90% (18/20) in the autologous iliac group, with no significant difference (χ(2)=0.176, P=0.675). Imaging review showed that grade Ⅰ bony fusion was obtained in both groups, and the fusion time of bone graft in the n-HA/PA66 group was significantly longer than that in the autologous iliac bone group (P0.05). No recurrence of tuberculosis, loosening or fracture of the internal fixator, or displacement of the bone graft was observed during follow-up. CONCLUSION: In elderly patients with lumbar spine tuberculosis, the n-HA/PA66 bioactive support combined with allogeneic bone graft can effectively restore and maintain the fusion segment height and physiological curvature of the lumbar spine, and the fusion rate of bone graft is similar to that of autologous iliac bone, which can achieve better effectiveness.

Cuprizone (CPZ) is a chemical chelator toxic to mitochondria of cells. While inducing oligodendrocyte (OL) loss and demyelination, CPZ caused no fatal damage to the other brain cells (neurons, astrocytes, and microglia) in previous studies, suggesting differential susceptibility and vulnerability of brain cells to the CPZ intoxication. To demonstrate this interpretation, C57BL/6 mice were fed rodent chow without or with CPZ (0.2%, w/w) for 7 days. One day later, mitochondrial function of brain cells was assessed by proton magnetic resonance spectroscopy (1H-MRS) and biochemical analysis. Another batch of mice were processed to localize the CPZ-induced damage to mitochondrial DNA, label brain cells, and identify apoptotic cells. Compared to controls, CPZ-exposed mice showed significantly lower levels of N-acetyl-L-aspartate, phosphocreatine, and ATP detected by 1H-MRS, indicating mitochondrial dysfunction in brain cells. Susceptibility analysis showed an order of OLs, microglia, and astrocytes from high to low, in terms of the proportion of 8-OHdG labeled cells in each type of these cells in corpus callosum. Vulnerability analysis showed the highest proportion of caspase-3 positive cells in labeled OLs in cerebral cortex and hippocampus, where neurons showed no caspase-3 labeling, but the highest proportion of 8-OHdG labeling, indicating a lowest vulnerability but highest susceptibility to CPZ-induced mitochondrial dysfunction. Immature OLs, microglia, and astrocytes showed adaptive changes in proliferation and activation in response to CPZ-exposure. These data for the first time demonstrated the CPZ-induced mitochondria dysfunction in brain cells of living mouse and specified the differential susceptibility and vulnerability of brain cells to the CPZ intoxication.

STUDY DESIGN A radiological study of type II Modic changes (MCs). OBJECTIVES The aim of this study was to determine the characteristics of type II MCs on fat suppression (FS) magnetic resonance (MR) images and its association with radiological disc degeneration. SUMMARY OF BACKGROUND DATA Type II MCs are common endplate signal changes on MR images. On the basis of limited histological samples, type II MCs are thought to be stable fat degeneration. FS technique on MR, which can quantify fat content, may be an alternative to explore the pathology of MCs. To date, however, the characteristics of type II MCs on FS sequence have not been studied. METHODS Lumbar MR images conducted in a single hospital during a defined period were reviewed to include those with type II MCs and FS images. On FS images, signal status of type II MCs was visually classified as suppressed or not-suppressed. Signal intensity of vertebral regions with and without MCs was measured quantitatively on T2-weighted (T2W) and FS images to calculate fat content index and validate the visual classification. Using image analysis program Osirix, MCs size and adjacent disc degeneration were measured quantitatively. Paired t-tests and logistic regressions were used to determine the associations studied. RESULTS Sixty-four lumbar MRIs were included and 150 endplates with type II MCs were studied. Although signal of 37 (24.7%) type II MCs was suppressed on FS images, that of 113 (75.3%) was not suppressed. The discs adjacent to type II MCs had lower signal intensity (0.13 ± 0.003 vs. 0.14 ± 0.004, P

Osteoarthritis (OA) is a degenerative joint disease characterized by joint destruction with cartilage loss and occasional gross derangement of joint integrity. In recent years, several studies have reported the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and knee OA. However, the results were conflicting. To determine the association between ACE gene I/D polymorphism and knee OA, we conducted a hospital-based case–control study with 282 knee OA cases and 316 controls to investigate the association between ACE gene I/D polymorphism and knee OA susceptibility in a Chinese Han population. The present study found that DD genotype or D allele carriers of ACE gene I/D polymorphism increased the risk of knee OA. Stratification analyses of sex, age, and body mass index (BMI) showed significant associations amongst the groups of females, ≥55 years, and abnormal BMI. In addition, the present study made analysis between ACE I/D polymorphism and some clinical features of OA, and found DD genotype of I/D polymorphism was associated with arthralgia. Furthermore, we undertook a meta-analysis together with the present study between this single nucleotide polymorphism (SNP) and knee OA risk. This meta-analysis found that ACE gene I/D polymorphism was associated with increased risk for OA. Stratification analysis of ethnicity in this meta-analysis indicated that I/D polymorphism increased the risk of knee OA amongst the Asians and Caucasians. In conclusion, this case–control study and meta-analysis suggest that ACE gene I/D polymorphism is associated with increased risk for knee OA.

This study aimed to evaluate the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings and pattern of FDG uptake in pancreatic metastases. A total of 19 consecutive patients (26 lesions) with histologically or clinically confirmed pancreatic metastases who had undergone 18F-FDG-PET/CT were enrolled in this retrospective study. Among the 19 patients, 14 patients underwent abdominal contrast-enhanced CT (ceCT). The location, size and FDG uptake patterns of the pancreatic lesions were recorded. Metabolic activity by means of maximum standardised uptake value (SUVmax) was measured by drawing regions of interest at the site of pancreatic lesions. Twenty pancreatic cancer patients were included in this study as comparative data analysis. The difference of SUVmax between pancreatic metastases and primary pancreatic cancer were compared using the Mann–Whitney U test. P 0.05). Four intrapancreatic isodense nodules in three patients were undetected on ceCT. The described patterns of FDG uptake findings may be helpful for a better characterisation of pancreatic metastases although semiquantitative analysis using SUVmax could not be used as a criterion for differentiating pancreatic metastases from primary pancreatic cancer. FDG-PET/CT has also an advantage in detecting unsuspected pancreatic metastases which cannot be detected by ceCT imaging. Thus, it is a useful adjunct to the described features on CT.

In this retrospective study, we evaluated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in differentiating malignant from benign portal vein thrombosis (PVT) in patients with known malignant tumors. Seventy-two patients with histologically or clinically confirmed PVT and who had undergone 18F-FDG PET/CT were included. Visual and semiquantitative analyses of PET/CT scans were performed. Metabolic activity was measured using the maximum standardized uptake value (SUVmax) by drawing the region of interest at the site of thrombosis. Receiver operating characteristic analysis was conducted to identify the optimal cutoff of SUVmax for detecting neoplastic thrombosis. Malignancy was defined using the following criteria: (1) visual analysis and (2) SUVmax >3.35. PET/CT results were confirmed with histopathological results and clinical and imaging follow-up. The SUVmax of tumor thrombus (6.37 ± 2.67) was significantly higher than that of bland thrombus (2.87 ± 1.47; P 3.35 as a criterion.

China has repeatedly been the subject of genetic studies to elucidate its prehistoric and historic demography. While some studies reported a genetic distinction between Northern and Southern Han Chinese, others showed a more clinal picture of small differences within China. Here, we investigated the distribution of Y chromosome variation along administrative as well as ethnic divisions in the mainland territory of the People's Republic of China, including 28 administrative regions and 19 recognized Chinese nationalities, to assess the impact of recent demographic processes. To this end, we analyzed 37,994 Y chromosomal 17-marker haplotype profiles from the YHRD database with respect to forensic diversity measures and genetic distance between groups defined by administrative boundaries and ethnic origin. We observed high diversity throughout all Chinese provinces and ethnicities. Some ethnicities, including most prominently Kazakhs and Tibetans, showed significant genetic differentiation from the Han and other groups. However, differences between provinces were, except for those located on the Tibetan plateau, less pronounced. This discrepancy is explicable by the sizeable presence of Han speakers, who showed high genetic homogeneity all across China, in nearly all studied provinces. Furthermore, we observed a continuous genetic North-South gradient in the Han, confirming previous reports of a clinal distribution of Y chromosome variation and being in notable concordance with the previously observed spatial distribution of autosomal variation. Our findings shed light on the demographic changes in China accrued by a fast-growing and increasingly mobile population.

We and other research groups have previously shown that various cancer types can express immunoglobulin G, but investigation on of immunoglobulin G expression in esophageal cancer, a highly malignant tumor, and its biological significance has been lacking. In this study, we examined immunoglobulin G protein and its messenger RNA, as well as the expressions of recombination-activating gene 1, recombination-activating gene 2, and activation-induced cytidine deaminase in 142 cases of esophageal cancer tissues, and 2 esophageal cancer cell lines (Eca109, SHEEC). We also compared their expressions with tumor grade and a proliferation marker, Ki67. We used immunohistochemistry, immunofluorescence, in situ hybridization, laser microdissection coupled with reverse transcriptase polymerase chain reaction, and Western blot analysis. We detected transcripts of immunoglobulin G 1 heavy-chain constant region, immunoglobulin-κ and λ-light chains, immunoglobulin G variable region, and recombination-activating genes 1 and 2 in both esophageal cancer tissues and cell lines, whereas activation-induced cytidine deaminase was not detected. No immunoglobulin G receptor subtypes were detected. Statistic analysis revealed that immunoglobulin G expression correlated well with tumor grades (P < .001) and with the proliferation marker Ki67 (P < .001). Our results indicate that human esophageal cancer cells are capable of synthesizing immunoglobulin G, which is likely involved in the growth and proliferation of this highly malignant cancer and might also be used as a prognostic indicator in esophageal squamous cell carcinomas.

The two hypervariable segments (HVS-I and HVS-II) of mitochondrial DNA (mtDNA) control region were sequenced for a population of 208 unrelated healthy individuals sampled from Suiping County, Henan Province, China. A total of 192 different haplotypes were identified, of which 179 haplotypes were unique (93.23%). The variation of the mtDNA HVS-I and HVS-II was confined to 166 nucleotide positions, of which 115 were observed in the HVS-I and 51 in the HVS-II. The haplotype diversity and random match probability were 0.9991 and 0.0061, respectively. Following the principle of the updated East Asian mtDNA phylogeny tree, individual samples were assigned to the specific haplogroups based on the information both from control region and coding-region obtained. Haplogroup D was the most common haplogroup (25.96%). The northern China-prevalent haplogroups (A, C, D, G, M8, Y, and Z) and the southern China-prevalent haplogroups (B, F, M7, N9, and R9) accounted for 48.56% and 46.63%, respectively, of the Henan Han mtDNA gene pool. The mtDNA hypervariable region was highly polymorphic in Henan Han population. These sequences could serve as mtDNA reference data for forensic casework in Henan population as well as for population genetic study.

To explore the diagnostic value of the cross-modality fusion images provided by positron emission tomography/computed tomography (PET/CT) and contrast-enhanced CT (CECT) for pancreatic cancer (PC).Data from 70 patients with pancreatic lesions who underwent CECT and PET/CT examinations at our hospital from August 2010 to October 2012 were analyzed. PET/CECT for the cross-modality image fusion was obtained using TureD software. The diagnostic efficiencies of PET/CT, CECT and PET/CECT were calculated and compared with each other using a χ(2) test. P0.05 was considered to indicate statistical significance.Of the total 70 patients, 50 had PC and 20 had benign lesions. The differences in the sensitivity, negative predictive value (NPV), and accuracy between CECT and PET/CECT in detecting PC were statistically significant (P0.05 for each). In 15 of the 31 patients with PC who underwent a surgical operation, peripancreatic vessel invasion was verified. The differences in the sensitivity, positive predictive value, NPV, and accuracy of CECT vs PET/CT and PET/CECT vs PET/CT in diagnosing peripancreatic vessel invasion were statistically significant (P0.05 for each). In 19 of the 31 patients with PC who underwent a surgical operation, regional lymph node metastasis was verified by postsurgical histology. There was no statistically significant difference among the three methods in detecting regional lymph node metastasis (P0.05 for each). In 17 of the 50 patients with PC confirmed by histology or clinical follow-up, distant metastasis was confirmed. The differences in the sensitivity and NPV between CECT and PET/CECT in detecting distant metastasis were statistically significant (P0.05 for each).Cross-modality image fusion of PET/CT and CECT is a convenient and effective method that can be used to diagnose and stage PC, compensating for the defects of PET/CT and CECT when they are conducted individually.

The S100 protein CP-10 (chemotactic protein, 10 kD), a potent chemotactic factor for murine and human polymorphonuclear cells (PMN) and murine monocytes, has been purified in small amounts from supernatants of activated murine spleen cells (Lackmann et al., 1992). To obtain a more abundant source of the protein, CP-10 was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The property of S100 proteins to undergo calcium-dependent conformational changes was used in a novel approach to optimize the release of recombinant (r) CP-10 by thrombin cleavage. Purified rCP-10 was characterized by amino-terminal sequence analysis and bioassays. Optimal chemotactic activity of rCP-10 for murine PMN and WEHI-265 monocytoid cells was 10(-11) M (native protein has optimal chemotactic activity between 10(-11) and 10(-13) M). Immunization of rabbits with the GST/CP-10 fusion protein bound to glutathione-agarose beads resulted in high titer, specific antibodies that neutralized CP-10-initiated chemotaxis and were suitable for immunoblotting. A combination of Western and Northern analyses identified CP-10 in murine peritoneal exudate PMN and macrophages, splenocytes, bone marrow cells, and WEHI-265 cells (all of myeloid origin), but not in thymus, liver, lung, 3T3 fibroblasts, EL4 lymphoma cells, or bEND 3 brain endothelial cells, indicating cell-specific regulation of CP-10 expression.

This study was undertaken to analyse the clinical characteristics and computed tomography (CT) imaging features of patients with pancreatic acinar cell carcinoma and to clarify characteristic imaging features.Clinical and CT imaging records of ten patients with pancreatic acinar cell carcinoma (three women and seven men; mean age, 58 years) examined using multidetector CT scanners were retrospectively studied. CT features emphasised included lesion location, size, shape, margin, solid or cystic component, density and enhancement. Imaging results were correlated with intraoperative surgical and pathological results.Lesions were distributed throughout the pancreatic head (n=3), body (n=3), tail (n=2) and both body and tail (n=2). The average diameter was 6.1 cm, varying from 2.3 cm to 15.8 cm. The tumours were round or oval (n=7) or lobular (n=3). Seven tumours appeared as enhanced solid pancreatic masses, with the large masses having hypodense areas; three had75 % cystic component; seven (70%), including four solid and three cystic masses, had well-circumscribed or partially well-defined thin, enhanced encapsulation. After contrast injection, the masses presented heterogeneous enhancement.Acinar cell carcinoma should always be considered when a large pancreatic mass with typical imaging is found in solid masses with variably sized central cystic areas or cystic masses.

The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP- 10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP- 10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run- on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.