Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

A rare complication of pelvic perforation by an excessive medial slide of the helical blade after treatment of an intertrochanteric fracture with proximal femoral nail anti-rotation: A case report and literature review.

Intertrochanteric fractures have become a severe public health problem in elderly patients. Proximal femoral nail anti-rotation (PFNA) is a commonly used intramedullary fixation device for unstable intertrochanteric fractures. Pelvic perforation by cephalic screw is a rare complication. We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture. The patient underwent surgery with PFNA as the intramedullary fixation device. Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation. We performed a cemented total hip arthroplasty as the savage procedure. At the latest follow-up of 12 months after total hip arthroplasty, the patient had no pain or loosening of the prosthesis in the left hip. Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device, especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation. The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.

[Perioperative Antiplatelet Therapy in Patients with Coronary Stents Undergoing Elective Non-Cardiac Surgery].

Among patients undergoing elective non-cardiac surgery (NCS), those with coronary stent implants are gradually becoming a patient group that cannot be easily overlooked. Previous history of heart disease, coronary stents and antiplatelet agents expose these patients to dual perioperative risks of thrombosis and bleeding. Formulating appropriate plans for perioperative antiplatelet therapy will help reduce the risks and ensure the safety of patients. We herein reviewed and analyzed various aspects of perioperative antiplatelet therapy for patients with coronary stent implants undergoing elective NCS, and discussed prospective research directions in the field.

The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

INTRODUCTION: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test. METHODS: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots. RESULTS: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%). CONCLUSION: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Postoperative Complications and Survival Analysis of Surgical Resection for Hilar Cholangiocarcinoma: A Retrospective Study of Fifty-Nine Consecutive Patients.

Objective Hilar cholangiocarcinoma (HC) is invariably fatal without surgical resection. The primary aim of the current study was to determine the safety of variable surgical resections for patient with HC and their survival after surgical resection. In addition, prognostic factor for the overall survival was also evaluated. Methods The study included 59 consecutive patients who were newly diagnosed with HC and underwent surgical resections with curative intend between February 2009 and February 2017. Patients were followed up at 3-6 months intervals after hospital discharge. Postoperative complications and overall survival were determined. Associations of clinicopathologic and surgeon-related factors with overall survival were evaluated through univariate analysis and Cox regression analysis. Results Of patients with Bismuth and Corlette (B & C) type Ⅲ (n=19) and Ⅳ (n=25) HC lesions, 33 (55.9%) were treated with hilar resection combined with major liver resection (MLR), while the other 11 patients with type Ⅲ and Ⅳ, and those with type Ⅰ (n=8) and Ⅱ (n=7) HC lesions were treated with hilar resection. The overall surgical mortality was 5.1% and surgical morbidity was 35.6%. There was no statistical difference in the mortality between MLR group and hilar resection group (6.1% vs. 3.8%; X2=0.703, P=0.145). The median follow-up period was 18 months (range, 1-94 months). The 1-, 3-, 5-year survival rate was 59.3%, 36.5%, and 17.7%, respectively. The overall survival after resections was 18 months. In HC patients with B & C type Ⅲ and Ⅳ lesions, the median survival was 23 months for hilar resection with MLR and 8 months for hilar resection alone; the 1-, 3-, 5-year cumulative survival rate was 63.9%, 23.3%, and 15.5%, respectively for hilar resection with MLR, and 11.1%, 0, and 0, respectively for hilar resection alone, with significant differene observed (HR, 9.902; 95% CI, 2.636-19.571, P=0.001). Four factors were independently associated with overall survival: preoperative serum Ca19-9 (HR, 7.039; 95% CI, 2.803-17.678, P<0.001), histopathologic grade (HR, 4.964; 95% CI, 1.046-23.552, P=0.044), surgical margins (P=0.031), and AJCC staging (P=0.015). Conclusions R0 resection is efficacious in surgical treatment of HC. MLR in combination with caudate lobe resection may increase the chance of R0 resection and improve survival of HC patients with B & C type Ⅲ and Ⅳ lesions. Preoperatively prepared for biliary drainage may ensure the safety of MLR in most HC patients. Novel adjuvant therapies are needed to improve the survival of HC patients with poor prognostic factors.

Chemokine CCL27 is a novel plasma biomarker for identification the nasopharyngeal carcinoma patients from the Epstein-Barr virus capsid antigen-specific IgA seropositive population.

BACKGROUND: To investigate the predictive value of chemokine CCL27 for identifying early stage nasopharyngeal carcinoma (NPC) patients within a population seropositive for Epstein-Barr virus (EBV) capsid antigen-specific IgA (VCA-IgA). METHODS: CCL27 in plasma samples from 104 NPC patients, 112 VCA-IgA-positive healthy donors, and 140 VCA-IgA-negative normal subjects was measured by ELISA. Expression of CCL27 in nasopharyngeal tissue from 20 VCA-IgA-positive healthy donors and 20 NPC patients was examined by immunohistochemical staining. RESULTS: Levels of CCL27 in the plasma of VCA-IgA-positive healthy donors (607.33 ± 218.81 pg/ml) were significantly higher than the levels in all NPC patients (437.09 ± 217.74, P = < 0.0001) and in the subset of patients with early stage NPC (463.85 ± 226.17, P = 0.0126). Plasma CCL27 levels were significantly lower in the VCA-IgA-negative normal subjects (358.22 ± 133.15 pg/ml) than in either the VCA-IgA-positive healthy donors (P < 0.0001) or the NPC patients (P = 0.0113). CCL27 protein was detected in 16 of 20 (80%) nasopharyngeal tissue samples from VCA-IgA-positive healthy donors and in 3 of 20 (15%) tumor tissue samples from NPC patients. There was no relationship between CCL27 levels and VCA-IgA titers or plasma EBV DNA content. Receiver operating characteristic (ROC) curves demonstrated that plasma CCL27 levels had a sensitivity of 67.00%, a specificity of 73.10%, and an area under the ROC of 0.725 (95% confidence interval [CI]: 0.657-0.793) for distinguishing between NPC patients and VCA-IgA-positive healthy donors. Further analysis showed that CCL27 levels could distinguish between early stage NPC patients and VCA-IgA-positive healthy donors with an area under the ROC of 0.712 (95% CI: 0.560-0.865), a sensitivity of 59.80%, and a specificity of 84.60%. CONCLUSIONS: Chemokine CCL27 could successfully identify NPC patients within a VCA-IgA-positive population.

A novel size-based sorting mechanism of pinocytic luminal cargoes in microglia.

Microglia are the resident immune cells in the CNS and play diverse roles in the maintenance of CNS homeostasis. Recent studies have shown that microglia continually survey the CNS microenvironment and scavenge cell debris and aberrant proteins by phagocytosis and pinocytosis, and that reactive microglia are capable to present antigens to T cells and initiate immune responses. However, how microglia process the endocytosed contents and evoke an immune response remain unclear. Here we report that a size-dependent selective transport of small soluble contents from the pinosomal lumen into lysosomes is critical for the antigen processing in microglia. Using fluorescent probes and water-soluble magnetic nanobeads of defined sizes, we showed in cultured rodent microglia, and in a cell-free reconstructed system that pinocytosed proteins become degraded immediately following pinocytosis and the resulting peptides are selectively delivered to major histocompatibility complex class II (MHC-II) containing lysosomes, whereas undegraded proteins are retained in the pinosomal lumen. This early size-based sorting of pinosomal contents relied on the formation of transient tunnel between pinosomes and lysosomes in a Rab7- and dynamin II-dependent manner, which allowed the small contents to pass through but restricted large ones. Inhibition of the size-based sorting markedly reduced proliferation and cytokine release of cocultured CD4(+) T cells, indicating that the size-based sorting is required for efficient antigen presentation by microglial cells. Together, these findings reveal a novel early sorting mechanism for pinosomal luminal contents in microglial cells, which may explain how microglia efficiently process protein antigens and evoke an immune response.

Effect of vaccination age on cost-effectiveness of human papillomavirus vaccination against cervical cancer in China.

BACKGROUND: The cost-effectiveness of human papillomavirus (HPV) vaccination in women pre-sexual debut has been demonstrated in many countries. This study aimed to estimate the cost-effectiveness of a 3-dose bivalent HPV vaccination at ages 12 to 55 year in both rural and urban settings in China. METHODS: The Markov cohort model simulated the natural history of HPV infection and included the effect of screening and HPV vaccination over the lifetime of a 100,000 female cohort. Transition probabilities and utilities were obtained from published literature. Cost data were estimated by Delphi panel using healthcare payers' perspective. Vaccine cost was assumed Hong Kong listed price. Vaccine efficacy (VE) was based on the PATRICIA trial data assuming VE irrespective of HPV type at all ages on incident HPV. Costs and outcomes were discounted at 3 %. Cervical cancer cases and incremental cost-effectiveness ratio (ICER) for vaccination and screening compared with screening alone were estimated for each vaccination age. Reduced VE in women post-sexual debut were investigated in scenario analyses. RESULTS: With 70 % vaccination coverage, a reduction of cancer cases varying from 585 to 33 in rural and 691 to 32 in urban were estimated at ages 12 to 55, respectively. The discounted ICERs of vaccination at any age under 23 years in rural and any age under 25 years in urban were lower than the current threshold. Scenario analyses with lower VE post-sexual debut confirmed the results with age 20 in rural and 21 in urban had consistent lower ICERs. The more 'catch-up' cohorts vaccinated at the start of a program, the more cancer lesions are avoided in the long-term. CONCLUSIONS: Vaccination at any age under 23 years old in rural and any age under 25 years old in urban were cost-effective. Catch-up to the age of 25 years in rural and urban could still be cost-effective.

Estimating long-term clinical effectiveness and cost-effectiveness of HPV 16/18 vaccine in China.

BACKGROUND: Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China. METHODS: A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China. RESULTS: Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8-119) in urban; and remained cost-effective when the vaccine cost ranged 630-1,700 CNY (US$ 100-270) in rural and 750-1,900 CNY (US$ 119-302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust. CONCLUSIONS: In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden.

Metal artifact reduction using virtual monochromatic images for patients with pedicle screws implants on CT.

PURPOSE: To evaluate the effect of spectral CT for metal artifact reduction in patients with pedicle screw. METHODS: 45 patients with 119 pairs of pedicle screws underwent spectral CT examination. One set of conventional (140 kVp) polychromatic image and nine sets of virtual monochromatic images (60-140 keV) were obtained. The standard deviation (SD) of CT number in 12 locations around the implant and 1 on homogenous fat was measured to generate artifact index (AI). Objective assessment including AI, CT number and SD value was performed with independent t test and paired sample t test. Two radiologists independently reviewed the image quality, and Wilcoxon signed-rank test and kappa analysis were used for the subjective scores of image quality. RESULTS: The artifact index (AI) of all the regions decreased as keV increased. AIs of 100-140 keV were lower than that of 140 kVp images. At 120 keV there was no significant difference in CT numbers of psoas major muscle and vertebral canal between pedicle screw level and pedicle level, but a significant difference in SD value was determined between the two levels. The subjective scores at 100-140 keV were higher than the images at 140 kVp, and the highest subjective score of two observers and excellent interobserver agreement were found at 120 keV (κ = 0.889). CONCLUSIONS: Virtual monochromatic images at high-energy levels have a well-concordant effect of removing metal artifacts, and 120 keV monochromatic images provided an accurate CT number and good subjective score.

A Novel Inflammation-Based Stage (I Stage) Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma.

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222-3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177-3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.

Hyperactive external awareness against hypoactive internal awareness in disorders of consciousness using resting-state functional MRI: highlighting the involvement of visuo-motor modulation.

Resting-state functional MRI (fMRI) has emerged as a valuable tool to characterize the complex states encompassing disorders of consciousness (DOC). Awareness appears to comprise two coexistent, anticorrelated components named the external and internal awareness networks. The present study hypothesizes that DOC interrupts the balance between the internal and external awareness networks. To gain more understanding of this phenomenon, the present study analyzed resting-state fMRI data from 12 patients with DOC versus 12 healthy age-matched controls. The data were explored using independent component analysis and amplitude of low-frequency fluctuation (ALFF) analysis. The results indicated that DOC deactivated midline areas associated with internal awareness. In addition, external awareness was strengthened in DOC because of increased activation in the insula, lingual gyrus, paracentral and supplementary motor area. The activity patterns suggested strengthened external awareness against weakened internal awareness in DOC. In particular, increased activity found in the insula, lingual gyrus, paracentral and supplementary motor area of patients with DOC implied possible involvement of augmented visuo-motor modulation in these patients. DOC is probably related to hyperactive external awareness opposing hypoactive internal awareness. This unique pattern of brain activity may potentially be a prognostic marker for DOC.

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

Evaluation of diagnostic efficacy of NRP-1/CD304 in hematological diseases.

BACKGROUND: Previous studies had explored the diagnostic or prognostic value of NRP-1/CD304 in blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and B-cell acute lymphoblastic leukemia (B-ALL), whereas the expression and application value of NRP-1/CD304 in other common hematological diseases have not been reported. METHODS: Bone marrow samples from 297 newly diagnosed patients with various hematological diseases were collected to detect the expression of NRP-1/CD304 by flow cytometry (FCM). The diagnostic efficacy of NRP-1/ CD304-positive diseases was analyzed by receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) was compared. RESULTS: In the research cohort, the total positive rate of NRP-1/CD304 was 14.81% (44/297), mainly distributed in BPDCN (100%, 6/6), B-ALL (48.61%, 35/72), and AML (4.48%, 3/67), with statistically significant differences (p < 0.01). Other diseases, such as T-cell acute lymphoblastic leukemia (T-ALL), B-cell non-Hodgkin lymphoma (B-NHL), T/NK-cell lymphoma and plasma cell neoplasms, did not express NRP-1/CD304. The AUC of NRP-1/CD304 was 0.936 (95% CI 0.898-0.973), 0.723 (95% CI 0.646-0.801), and 0.435 (95% CI 0.435) in BPDCN, B-ALL and AML, respectively. Besides, CD304 was commonly expressed in B-ALL with BCR-ABL1 gene rearrangement (p = 0.000), and CD304 expression was positively correlated with CD34 co-expression (p = 0.009) and CD10 co-expression (p = 0.007). CONCLUSIONS: NRP-1/CD304 is only expressed in BPDCN, B-ALL and AML, but not in other common hematological diseases. This indicates that NRP-1/CD304 has no obvious diagnostic and follow-up study value in hematological diseases other than BPDCN, B-ALL, and AML.

Association Between Perivascular Adipose Tissue Density and Atherosclerosis in the Descending Thoracic Aorta.

Radiodensity measured by computed tomography (CT) in Hounsfield Units (HU) is emerging as a clinical tool for detecting perivascular adipose tissue (PVAT) inflammation. In the present study, we hypothesized that PVAT radiodensity might predict the risk of descending thoracic aorta atherosclerosis. A total of 73 subjects who underwent CT angiography to investigate aortic disease were retrospectively analyzed. PVAT radiodensity, aortic complex plaque (ACP), mean plaque-burden score (MPBS), and plaque density were measured, and the association between them was analyzed. Perivascular adipose tissue radiodensity (HU) in patients with different aortic plaques grades (grade 1, 2, 3, and 4) were -93.71 ± 2.50, -93.63 ± 3.93, -90.24 ± 4.49, and -89.90 ± 5.18, respectively, and the difference was significant (P = .010). In the regression analysis, PVAT radiodensity was an independent predictor of ACP, with an OR of 1.263. In the linear analysis, PVAT radiodensity was an independent predictor of MPBS, with a ß-coefficient of .073. In the univariate analysis, only the PVAT radiodensity was significantly associated with plaque density, with a ß-coefficient of -1.666. In conclusion, PVAT density was independently related to descending thoracic aorta atherosclerosis.

Implementation of Individualized Low-Dose Computed Tomography-Guided Hook Wire Localization of Pulmonary Nodules: Feasibility and Safety in the Clinical Setting.

Background: CT-guided hook-wire localization is an essential step in the management of small pulmonary nodules. Few studies, however, have focused on reducing radiation exposure during the procedure. Purpose: This study aims to explore the feasibility of implementing a low-dose computed tomography (CT)-guided hook wire localization using tailored kVp based on patients' body size. Materials and Methods: A total of 151 patients with small pulmonary nodules were prospectively enrolled for CT-guided hook wire localization using individualized low-dose CT (LDCT) vs. standard-dose CT (SDCT) protocols. Radiation dose, image quality, characteristics of target nodules and procedure-related variables were compared. All variables were analyzed using Chi-Square and Student's t-test. Results: The mean CTDIvol was significantly reduced for LDCT (for BMI ≤ 21 kg/m2, 0.56 ± 0.00 mGy and for BMI > 21 kg/m2, 1.48 ± 0.00 mGy) when compared with SDCT (for BMI ≤ 21 kg/m2, 5.24 ± 0.95 mGy and for BMI > 21 kg/m2, 6.69 ± 1.47 mGy). Accordingly, the DLP of LDCT was significantly reduced as compared with that of SDCT (for BMI ≤ 21 kg/m2, 56.86 ± 4.73 vs. 533.58 ± 122.06 mGy.cm, and for BMI > 21 kg/m2, 167.02 ± 38.76 vs. 746.01 ± 230.91 mGy.cm). In comparison with SDCT, the effective dose (ED) of LDCT decreased by an average of 89.42% (for BMI ≤ 21 kg/m2) and 77.68% (for BMI > 21 kg/m2), respectively. Although the images acquired with the LDCT protocol yielded inferior quality to those acquired with the SDCT protocol, they were clinically acceptable for hook wire localization. Conclusions: LDCT-guided localization can provide safety and nodule detection performance comparable to SDCT-guided localization, benefiting radiation dose reduction dramatically, especially for patients with small body mass indexes.

A nerve conduit filled with Wnt5a-loaded fibrin hydrogels promotes peripheral nerve regeneration.

AIMS: Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect. METHODS: The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight. RESULTS: We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation. CONCLUSION: The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.

Association between exposures to phthalate metabolites and preterm birth and spontaneous preterm birth: A systematic review and meta-analysis.

Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.

Associations Between Polybrominated Diphenyl Ethers Concentrations in Human Placenta and Small for Gestational Age in Southwest China.

BACKGROUND: Prenatal exposures to polybrominated diphenyl ethers (PBDEs) may affect fetal growth. Small for gestational age (SGA) is a measure based on birth weight and gestational age at birth and represents a good indicator of fetal growth but it has been used only in a small number of studies. The present study aimed to examine the associations between PBDEs exposure and the risk of SGA among participants from a birth cohort in Southwest China. METHODS: The concentrations of eight common PBDE congeners (BDE-28, BDE47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209) in 996 human placental samples collected between May to October 2020 were determined. A questionnaire survey was administered regarding maternal characteristics. The outcome data of the newborns were obtained from the medical record. The Mann-Whitney U test and binomial logistic regression analysis were used to assess associations between PBDEs concentrations (as a continuous or categorical variable) and SGA. RESULTS: All PBDE congeners were detected in more than 73% of samples. The median concentrations of ΣPBDEs were 10.08 ng/g lipid weight (lw). BDE-209 was the most abundant PBDE congener, contributed 28% to ΣPBDEs. There were 114 (11.4%) SGA infants. The levels of BDE-99, BDE-100, BDE-209, and the total levels of ΣPBDEs in the SGA group were significantly higher than those in the controls. When classifying the PBDEs concentrations as two categories: low and high, high level of ΣPBDEs was associated with increased risk of SGA [odds ratio (OR): 2.203, 95% confidence interval (CI): 1.453-3.340] after adjusting for potential covariates. The association remained significant when stratifying the data by gender of the newborn (OR: 2.572, 95% CI: 1.337-4.947 for boys; OR: 2.385, 95% CI: 1.315-4.325 for girls). CONCLUSION: The present study adds to the literature by using placenta to measure PBDEs exposure during pregnancy, and provides evidence that prenatal exposure to PBDEs may be associated with the risk of SGA, at least at the levels of exposure in our population.

Tuberculosis treatment delay and nosocomial exposure remain important risks for patients undergoing regular hemodialysis.

BACKGROUND AND OBJECTIVE: Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS: Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS: Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p < 0.001). Nosocomial exposure increased active TB risk (adjusted odds ratio [OR; 95% confidence interval, CI]: 1.60 [1.55-1.66] per month of exposure), particularly when the exposure time was either within 6 months before the index case was diagnosed or 6-15 months before the ESRD patient became an incident active TB case. For patients with active TB, cough-related medication prescriptions (proxy for cough symptoms) exponentially increased over 6 months before TB treatment. CONCLUSION: Nosocomial exposure attributed to delay in the diagnosis of index pulmonary TB is important in TB transmission among patients undergoing regular hemodialysis. Additional studies investigating how TB can be diagnosed and treated early are warranted. SUMMARY AT A GLANCE: Our study revealed that nosocomial exposure, attributed to delay in pulmonary TB diagnosis, is important in TB transmission among patients undergoing regular hemodialysis. Strategies to diagnose and treat TB early are crucial to infection control, and they warrant further investigations.