Mdka produced by the activated HSCs drives bipotential progenitor cell redifferentiation during zebrafish biliary-mediated liver regeneration.

BACKGROUND AND AIMS: After extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs through trans-differentiation of biliary epithelial cells (BECs), which involves dedifferentiation of biliary epithelial cells into bipotential progenitor cells (BP-PCs) and subsequent redifferentiation of BP-PCs into nascent hepatocytes and biliary epithelial cells. Despite several studies on the redifferentiation process of BP-PCs into nascent hepatocytes, the contributions of nonparenchymal cells in this process remain poorly understood. APPROACH AND RESULTS: Using the zebrafish severe liver injury model, we observed specific expression of midkine a (Mdka) in the activated HSCs through single-cell analyses and fluorescence in situ hybridization. Genetic mutation, pharmacological inhibition, whole-mount in situ hybridizations, and antibody staining demonstrated an essential role of mdka in the redifferentiation of BP-PCs during liver regeneration. Notably, we identified Nucleolin (Ncl), the potential receptor for Mdka, specifically expressed in BP-PCs, and its mutant recapitulated the mdka mutant phenotypes with impaired BP-PC redifferentiation. Mechanistically, the Mdka-Ncl axis drove Erk1 activation in BP-PCs during liver regeneration. Furthermore, overexpression of activated Erk1 partially rescued the defective liver regeneration in the mdka mutant. CONCLUSIONS: The activated HSCs produce Mdka to drive the redifferentiation process of BP-PCs through activating Erk1 during the biliary-mediated liver regeneration, implying previously unappreciated contributions of nonparenchymal cells to this regeneration process.

Coordination Engineering of Heteronuclear Fe-Mo Dual-Atom Catalyst for Promoted Electrocatalytic Nitrogen Fixation: A DFT Study.

Developing efficient nanostructured electrocatalysts for N2 reduction to NH3 under mild conditions remains a major challenge. The Fe-Mo cofactor serves as the archetypal active site in nitrogenase. Inspired by nitrogenase, we designed a series of heteronuclear dual-atom catalysts (DACs) labeled as FeMoN6-a Xa (a=1, 2, 3; X=B, C, O, S) anchored on the pore of g-C3 N4 to probe the impact of coordination on FeMo-catalyzed nitrogen fixation. The stability, reaction paths, activity, and selectivity of 12 different FeMoN6-a Xa DACs have been systematically studied using density functional theory. Of these, four DACs (FeMoN5 B1 , FeMoN5 O1 , FeMoN4 O2 , and FeMoN3 C3 ) displayed promising nitrogen reduction reaction (NRR) performance. Notably, FeMoN5 O1 stands out with an ultralow limiting potential of -0.11 V and high selectivity. Analysis of the density of states and charge/spin changes shows FeMoN5 O1 's high activity arises from optimal N2 binding on Fe initially and synergy of the FeMo dimer enabling protonation in NRR. This work contributes to the advancement of rational design for efficient NRR catalysts by regulating atomic coordination environments.

Latest Progress of LIPUS in Fracture Healing: A Mini-Review.

The use of low-intensity pulsed ultrasound (LIPUS) for promoting fracture healing has been Food and Drug Administration (FDA)-approved since 1994 due to largely its non-thermal effects of sound flow sound radiation force and so on. Numerous clinical and animal studies have shown that LIPUS can accelerate the healing of fresh fractures, nonunions, and delayed unions in pulse mode regardless of LIPUS devices or circumstantial factors. Rare clinical studies show limitations of LIPUS for treating fractures with intramedullary nail fixation or low patient compliance. The biological effect is achieved by regulating various cellular behaviors involving mesenchymal stem/stromal cells (MSCs), osteoblasts, chondrocytes, and osteoclasts and with dose dependency on LIPUS intensity and time. Specifically, LIPUS promotes the osteogenic differentiation of MSCs through the ROCK-Cot/Tpl2-MEK-ERK signaling. Osteoblasts, in turn, respond to the mechanical signal of LIPUS through integrin, angiotensin type 1 (AT1), and PIEZO1 mechano-receptors, leading to the production of inflammatory factors such as COX-2, MCP-1, and MIP-1ß fracture repair. LIPUS also induces CCN2 expression in chondrocytes thereby coordinating bone regeneration. Finally, LIPUS suppresses osteoclast differentiation and gene expression by interfering with the ERK/c-Fos/NFATc1 cascade. This mini-review revisits the known effects and mechanisms of LIPUS on bone fracture healing and strengthens the need for further investigation into the underlying mechanisms.

Duhamel and transanal endorectal pull-throughs for Hirschsprung disease: a Bayesian network meta-analysis.

BACKGROUND: To comprehensively compare the effects of open Duhamel (OD), laparoscopic-assisted Duhamel (LD), transanal endorectal pull-through (TEPT), and laparoscopic-assisted endorectal pull-through (LEPT) in Hirschsprung disease. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched up to August 4, 2022. The outcomes were operation-related indicators and complication-related indicators. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence. Network plots, forest plots, league tables and rank probabilities were drawn for all outcomes. For measurement data, weighted mean differences (WMDs) and 95% credibility intervals (CrIs) were reported; for enumeration data, relative risks (RRs) and 95%CrIs were calculated. RESULTS: Sixty-two studies of 4781 patients were included, with 2039 TEPT patients, 1669 LEPT patients, 951 OD patients and 122 LD patients. Intraoperative blood loss in the OD group was more than that in the LEPT group (pooled WMD = 44.00, 95%CrI: 27.33, 60.94). Patients lost more blood during TEPT versus LEPT (pooled WMD = 13.08, 95%CrI: 1.80, 24.30). In terms of intraoperative blood loss, LEPT was most likely to be the optimal procedure (79.76%). Patients undergoing OD had significantly longer gastrointestinal function recovery time, as compared with those undergoing LEPT (pooled WMD = 30.39, 95%CrI: 16.08, 44.94). The TEPT group had significantly longer gastrointestinal function recovery time than the LEPT group (pooled WMD = 11.49, 95%CrI: 0.96, 22.05). LEPT was most likely to be the best operation regarding gastrointestinal function recovery time (98.28%). Longer hospital stay was observed in patients with OD versus LEPT (pooled WMD = 5.24, 95%CrI: 2.98, 7.47). Hospital stay in the TEPT group was significantly longer than that in the LEPT group (pooled WMD = 1.99, 95%CrI: 0.37, 3.58). LEPT had the highest possibility to be the most effective operation with respect to hospital stay. The significantly reduced incidence of complications was found in the LEPT group versus the LD group (pooled RR = 0.24, 95%CrI: 0.12, 0.48). Compared with LEPT, OD was associated with a significantly increased incidence of complications (pooled RR = 5.10, 95%CrI: 3.48, 7.45). Patients undergoing TEPT had a significantly greater incidence of complications than those undergoing LEPT (pooled RR = 1.98, 95%CrI: 1.63, 2.42). For complications, LEPT is most likely to have the best effect (99.99%). Compared with the LEPT group, the OD group had a significantly increased incidence of anastomotic leakage (pooled RR = 5.35, 95%CrI: 1.45, 27.68). LEPT had the highest likelihood to be the best operation regarding anastomotic leakage (63.57%). The incidence of infection in the OD group was significantly higher than that in the LEPT group (pooled RR = 4.52, 95%CrI: 2.45, 8.84). The TEPT group had a significantly increased incidence of infection than the LEPT group (pooled RR = 1.87, 95%CrI: 1.13, 3.18). LEPT is most likely to be the best operation concerning infection (66.32%). Compared with LEPT, OD was associated with a significantly higher incidence of soiling (pooled RR = 1.91, 95%CrI: 1.16, 3.17). Patients with LEPT had the greatest likelihood not to develop soiling (86.16%). In contrast to LD, LEPT was significantly more effective in reducing the incidence of constipation (pooled RR = 0.39, 95%CrI: 0.15, 0.97). LEPT was most likely not to result in constipation (97.81%). LEPT was associated with a significantly lower incidence of Hirschprung-associated enterocolitis (HAEC) than LD (pooled RR = 0.34, 95%CrI: 0.13, 0.85). The OD group had a significantly higher incidence of HAEC than the LEPT group (pooled RR = 2.29, 95%CrI: 1.31, 4.0). The incidence of HAEC was significantly greater in the TEPT group versus the LEPT group (pooled RR = 1.74, 95%CrI: 1.24, 2.45). LEPT was most likely to be the optimal operation in terms of HAEC (98.76%). CONCLUSION: LEPT may be a superior operation to OD, LD and TEPT in improving operation condition and complications, which might serve as a reference for Hirschsprung disease treatment.

Global research trends in CRISPR-related technologies associated with extracellular vesicles from 2015 to 2022: a bibliometric, dynamic, and visualized study.

PURPOSE: This study aims to explore the emerging trends, dynamic development, and research hotspots of clustered regularly interspaced short palindromic repeats (CRISPR) technology associated with extracellular vesicles during the past 7 years and demonstrate them by visualization. METHODS: A total of 219 records related to CRISPR technology associated with extracellular vesicles from 2015 to 2022 in the Web of Science Core Collection (WoSCC) database were collected. R language, VOSviewer, CiteSpace, and GraphpadPrism software packages were used to analyze the history of this research, the general characteristics of the literature, and keywords. Finally, the hotspots and latest trends in CRISPR technology associated with extracellular vesicles are predicted. RESULTS: A total of 219 articles were collected for this study. The production of publications about CRISPR technology associated with extracellular vesicles has increased annually. Researchers from China, the USA, and Germany made the most important contributions to this trend, while RLUK Research Libraries UK offers the largest amount of literature in this field. Shenzhen University, Nanjing Medicine University, and Peking University exhibited the closest cooperation. Additionally, active topics burst during different periods, as identified according to 317 keywords belonging to 39 disciplines. Keywords were clustered into seven research subareas, namely exosome, nanovesicles, DNA, gene editing, gene therapy, cancer therapy, and endometrial stromal cells. The alluvial map of keywords reveals that the most enduring concepts are gene therapy, nanovesicles, etc., while the emerging keywords are genome, protein delivery, plasma, etc. CONCLUSIONS: We reviewed 219 previous publications and conducted the first bibliometric study of CRISPR technology related to extracellular vesicles from 2015 to 2022. This comprehensive summary constructed a knowledge map and demonstrates the trends in this area. The current trends and potential hotpots for this topic are also identified, which will be a great help for researchers in the future.

Synthetic CRISPR/dCas9-KRAB system driven by specific PSA promoter suppresses malignant biological behavior of prostate cancer cells through negative feedback inhibition of PSA expression.

PSA is a type of proto-oncogene that is specifically and highly expressed in embryonic and prostate cancer cells, but not expressed in normal prostate tissue cells. The specific expression of prostate-specific antigen (PSA) is found to be related with the conditional transcriptional regulation of its promoter. Clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-KRAB is a newly developed transcriptional regulatory system that inhibits gene expression by interupting the DNA transcription process. Induction of CRISPR-dCas9-KRAB expression through the PSA promoter may help feedback inhibition of cellular PSA gene expression via single guide RNA (sgRNA), thereby monitoring and suppressing the malignant state of tumor cells. In this study, we examined the transcriptional activity of the PSA promoter in different prostate cancer cells and normal prostate epithelial cells and determined that it is indeed a prostate cancer cell-specific promoter.Then we constructed the CRISPR-dCas9-KRAB system driven by the PSA promoter, which can inhibit PSA gene expression in the prostate cancer cells at the transcriptional level, and therefore supress the malignant growth and migration of prostate cancer cells and promote their apoptosis in vitro. This study provides a potentially effective anti-cancer strategy for gene therapy of prostate cancer.

Achilles tendon thickening does not affect elasticity and functional outcome after surgical repair of Achilles rupture: A retrospective study.

PURPOSE: Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function. METHODS: In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference. RESULTS: AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm2 than that at 3 months postoperatively ((278.0 ± 26.2) mm2, t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm2, t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period. CONCLUSION: Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference.

[Analysis of Imaging Performance Standards of CBCT X-IGRT System Used in Radiotherapy].

This article briefly describes the imaging performance standards of the kilovolt X-ray image guidance system used in radiotherapy, analyzes the main aspects that should be considered in the image quality of X-IGRT system, and focuses on parameters that should be considered in the imaging performance evaluation criteria of the CBCT X-IGRT. The purpose is to sort out the imaging performance evaluation standards of kilovolt X-IGRT system, clarify the image quality requirements of X-IGRT equipment, and reach a consensus when evaluating the imaging performance of X-IGRT system.

Quantitative MR evaluation of the infrapatellar fat pad for knee osteoarthritis: using proton density fat fraction and T2* relaxation based on DIXON.

OBJECTIVES: To investigate the efficacy of fat fraction (FF) and T2* relaxation based on DIXON in the assessment of infrapatellar fat pad (IFP) for knee osteoarthritis (KOA) progression in older adults. METHODS: Ninety volunteers (age range 51-70 years, 65 females) were enrolled in this study. Participants were grouped based on the Kellgren-Lawrence grading (KLG). The FF and T2* values were measured based on the 3D-modified DXION technique. Cartilage defects, bone marrow lesions, and synovitis were assessed based on a modified version of whole-organ magnetic resonance imaging score (WORMS). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. The differences of FF and T2* measurement and the correlation with WORMS and WOMAC assessments were analyzed. Diagnostic efficiency was analyzed by using receiver operating characteristic (ROC) curves. RESULTS: A total of 60 knees were finally included (n = 20 in each group). The values were 82.6 ± 3.7%, 74.7 ± 5.4%, and 60.5 ± 14.1% for FF is the no OA, mild OA, and advanced OA groups, and were 50.7 ± 6.6 ms, 44.1 ± 6.6 ms, and 39.1 ± 4.2 ms for T2*, respectively (all p values < 0.001). The WORMS assessment and WOMAC pain assessment showed negative correlation with FF and T2* values. The ROC showed the area under the curve (AUC), sensitivity, and specificity for diagnosing OA were 0.93, 77.5%, and 100% using FF, and were 0.86, 75.0%, and 90.0% using T2*, respectively. CONCLUSIONS: FF and T2* alternations in IFP are associated with knee structural abnormalities and clinical symptoms cross-sectionally and may have the potential to predict the severity of KOA. KEY POINTS: • Fat fraction (FF) and T2* relaxation based on DIXON imaging are novel methods to quantitatively assess the infrapatellar fat pad for knee osteoarthritis (KOA) progression in older adults. • The alterations of FF and T2* using mDIXON technique in IFP were associated with knee structural abnormalities and clinical symptoms. • FF and T2* alternations in IFP can serve as the new imaging biomarkers for fast, simple, and noninvasive assessment in KOA.

MELD-XI score predict no-reflow phenomenon and short-term mortality in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

INTRODUCTION: No-reflow phenomenon (NRP) is one of the complications that mostly occur during percutaneous coronary intervention (PCI). In this study, we comprehensively examined the relationship between the model for end-stage liver disease-XI (MELD-XI) score and NRP. Moreover, we discussed whether the MELD-XI score could be considered as an accurate risk assessment score of patients with ST-segment elevation myocardial infarction (STEMI) who are candidates for PCI. METHODS: This retrospective study involved 693 patients with acute STEMI and who underwent an emergency PCI. They were divided into a normal reflow group or a no-reflow group on the basis of the flow rate of post-interventional thrombolysis in myocardial infarction. Univariate, multivariate logistic regression, and Cox regression analyses were performed to identify the independent predictors of NRP in both groups. Receiver operator characteristic (ROC) curves and Kaplan-Meier curves were plotted to estimate the predictive values of the MELD-XI score. RESULTS: MELD-XI score was found to be an independent indicator of NRP (odds ratio: 1.247, 95% CI: 1.144-1.360, P < 0.001). Multivariate Cox regression analysis also revealed that the MELD-XI score is an independent prognostic factor for 30-day all-cause mortality (hazard ratio: 1.155, 95% CI: 1.077-1.239, P < 0.001). Moreover, according to the ROC curves, the cutoff value of the MELD-XI score to predict NRP was 9.47 (area under ROC curve: 0.739, P < 0.001). The Kaplan-Meier curves for 30-day all-cause mortality revealed lower survival rate in the group with a MELD-XI score of > 9.78 (P < 0.001). CONCLUSION: The MELD-XI score can be used to predict NRP and the 30-day prognosis in patients with STEMI who are candidates for primary PCI. It could be adopted as an inexpensive and a readily available tool for risk stratification.

Multifunctional injectable hydrogel for effective promotion of cartilage regeneration and protection against osteoarthritis: combined chondroinductive, antioxidative and anti-inflammatory strategy.

The regeneration of the articular cartilage defects is characterized by the improvement in the quality of the repaired tissue and the reduction in the potential development of perifocal osteoarthritis (OA). Usually, the injection of dexamethasone (Dex) in the OA joints slows down the progression of inflammation and relieves pain. However, the anti-inflammatory Dex injected in the joint cavity is rapidly cleared, leading to a poor therapeutic effect. Multifunctional hydrogels with simultaneous chondrogenic differentiation, antioxidative, and anti-inflammatory capacities may represent a promising solution. Therefore, in this work, a novel injectable hydrogel based on double cross-linking of Schiff base bonds and coordination of catechol-Fe was developed. The obtained hydrogel (Gel-DA/DOHA/DMON@Dex@Fe) possessed molding performance in situ, excellent mechanical strength, controllable biodegradability, the on-demand release of the drug, and biocompatibility. The hydrogel system stimulated the HIF-1α signaling pathway and suppressed inflammation thanks to the introduction of DMON@Fe, consequently facilitating chondrogenic differentiation. The synergistic anti-inflammatory effect together with the induction of chondrogenesis by Dex-loaded Gel-DA/DOHA/DMON@Fe hydrogel allowed the promotion of cartilage repair, as demonstrated by in vivo experiments. Hence, the proposed multifunctional scaffold provides a promising advancement in articular cartilage tissue engineering and may have great prospects in the prevention of OA.

[Analysis on the Quality Status of in Vitro Diagnostic Reagents for National Medical Device Supervision and Inspection in 2020].

OBJECTIVE: This paper puts forward suggestions on the development of in vitro diagnostic reagents and supervision measures for the post-marketing products, so as to further improve the quality of in vitro diagnostic reagents and ensure the safety use of medical device. METHODS: This paper summarizes the quality of in vitro diagnostic reagents and analyzes the causes of the problems, according to the results of the national medical device supervision and inspection in 2020. RESULTS: The overall quality of in vitro diagnostic reagents for national medical device supervision and inspection in 2020 is stable and the unqualified detection rate is 1.6%. However, there are some problems. For example, the management of raw materials is unscientific, the faultiness in the preparation of reference materials, the understanding of standards is unthorough, and the management of instructions is unimportance. CONCLUSIONS: It is suggested that manufacturers of in vitro diagnostic reagents should improve the binding force of the quality management system, strengthen the awareness of risk management, attach importance to communicate with regulatory authorities, study standards sufficiently and strengthen the management of instructions. It is also suggested that the regulatory authorities should strengthen supervision and inspection, and further complete the evaluation guidance and standard publicity and implementation.

[Analysis on the Characteristics of Quality Variation of National Medical Device Supervision and Inspection in 2020].

This study is based on the summary of the characteristics of quality variation of national medical device supervision and inspection in 2020. According to the results of the national medical device supervision and inspection through comparative analysis, this study puts forward suggestions on the medical device production and supervision measures for the post-marketing products, so as to further improve the level of the medical device and ensure the safety use of medical device.

Anatomical knee variables result in worse outcomes of lateral meniscal allograft transplantation with discoid lateral menisci than with nondiscoid lateral menisci.

PURPOSE: To compare the clinical results of meniscal allograft transplantation (MAT) between patients with discoid lateral meniscus (DLM) and non-DLM (NDLM) and to analyse whether anatomical deformities cause worse clinical results in DLM patients. METHODS: Patients who underwent unilateral MAT from 2005 to 2017, including 115 patients with DLMs or NDLMs, were included in this study. Clinical outcomes [International Knee Documentation Committee (IKDC) scores, Lysholm scores, Tegner scores, and visual analogue scale (VAS) scores] and radiographic and MRI data were assessed. Clinical outcomes and anatomical knee variables were analysed by multivariate stepwise regression. RESULTS: After more than 2 years of follow-up, 9 patients were lost to follow-up, and 59 patients with DLM and 47 patients with NDLM were included. The mean postoperative results were significantly better than the preoperative data (P < 0.05) in both the DLM and NDLM groups. In addition, postoperative IKDC, Lysholm, and VAS scores but not Tegner scores were better in the NDLM group than in the DLM group. Several anatomical knee variables differed significantly between the NDLM and DLM groups and were associated with MAT outcomes. The condylar prominence ratio of the lateral and medial femoral condyles adjacent to the intercondylar notch and squaring of the lateral femoral condyle (the distance of the straight articular condylar surface) were independent factors significantly correlated with the Lysholm scores for MAT at last follow-up. CONCLUSION: MAT improved knee function in both patients with DLM and patients with NDLM, but patients NDLM had better clinical outcomes than patients with DLM. The condylar prominence ratio and squaring of the lateral femoral condyle may underlie this result. LEVEL OF EVIDENCE: III.

[Analysis of Quality Status of National Medical Device Supervision and Inspection in 2019].

Summarize the quality status and variety quality change characteristics of the sampling products through the Summary and analysis, according to the results of the national medical device supervision and inspection in 2019. Put forward suggestions on the development of the medical device industry and supervisory measures. Thereby, further improve the level of the medical device and ensure the safety use of medical device.

Prediction of Abnormal Bone Density and Osteoporosis From Lumbar Spine MR Using Modified Dixon Quant in 257 Subjects With Quantitative Computed Tomography as Reference.

BACKGROUND: Bone marrow fat increases when bone mass decreases, which could be attributed to the fact that adipogenesis competes with osteogenesis. Bone marrow fat has the potential to predict abnormal bone density and osteoporosis. PURPOSE: To investigate the predictive value of using vertebral bone marrow fat fraction(BMFF) obtained from modified Dixon(mDixon) Quant in the determination of abnormal bone density and osteoporosis. STUDY TYPE: Prospective. POPULATION: 257 subjects (age: 20-79 years old; BMI: 16.6-32.9 kg/m2 ;181 females,76 males) without known spinal tumor, history of trauma, dysplasia, spinal surgery or hormone therapy. FIELD STRENGTH/SEQUENCE: 3.0T/mDixon. ASSESSMENT: BMFF was measured at the L1, L2 and L3 vertebral body on fat fraction maps of the lumbar spine. Bone mineral density (BMD) was obtained using quantitative computed tomography, which served as the reference standard. STATISTICAL TESTS: The BMFF between the three groups (normal bone density, osteopenia and osteoporosis) was tested using one-way analysis of variance in SPSS. The correlation and partial correlation of BMFF and BMD were analyzed before and after controlling for age, sex and BMI. Logistic regression analysis using independent training and validation data was conducted to evaluate the performance of predicting abnormal BMD or osteoporosis using BMFF. RESULTS: There was a significant difference in vertebral BMFF between the three groups (P < 0.001). Moderate inverse correlation was found between vertebral BMFF and BMD after controlling age, sex and BMI (r = -0.529; P < 0.001). The mean area under the curve, sensitivity, specificity and negative predictive value (NPV) for predicting abnormal bone density were 0.940, 0.877, 0.896, and 0.890, respectively. The corresponding results for predicting subjects with osteoporosis were 0.896, 0.848, 0.853, and 0.969, respectively. DATA CONCLUSION: mDixon Quant is a fast, simple, noninvasive and nonionizing method to access vertebral BMFF and has a high predictive power for identifying abnormal bone density and osteoporosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:390-399.

Magnetic Susceptibility and Fat Content in the Lumbar Spine of Postmenopausal Women With Varying Bone Mineral Density.

BACKGROUND: Osteoporosis is a systemic disease characterized by low bone mass with increased fracture risk. Quantitative imaging biomarkers are important for accurately predicting fracture risk in patients with osteoporosis. PURPOSE: To prospectively study the changes of magnetic susceptibility and fat content in the lumbar spine of postmenopausal females with varying bone mineral density (BMD), and investigate their application to osteoporosis assessment. STUDY TYPE: Cohort. POPULATION: In all, 108 postmenopausal females (58.2 ± 6.7 [range 45-79] years old). FIELD STRENGTH/SEQUENCE: Quantitative computed tomography (QCT) performed on a 64-detector CT scanner; quantitative susceptibility mapping (QSM) and mDixon quant MR imaging performed using a 3.0T imaging system with a 16-channel posterior coil. ASSESSMENT: QCT, QSM, and mDixon were performed in 108 postmenopausal females to measure vertebral BMD, susceptibility, and proton-density fat fraction (PDFF). Mean vertebral QSM and PDFF were compared among three BMD cohorts (normal, osteopenic, and osteoporotic). Receiver operating characteristic analyses were performed to evaluate the performance of QSM, PDFF, and QSM+PDFF for assessing osteoporosis. STATISTICAL TESTS: Parameters were compared using Kruskal-Wallis test and Pearson test. RESULTS: Compared with that of the normal BMD group (-17.0 ± 43.6 ppb), vertebral QSM was significantly increased in osteopenia (30.8 ± 47.0 ppb, P < 0.001), and further increased in osteoporosis (82.0 ± 39.9 ppb, P < 0.001). QSM was negatively correlated with BMD (r = -0.70, P < 0.001) and positively correlated with PDFF (r = 0.64, P < 0.001). Compared with the area under the curve (AUC) of PDFF, the AUC of QSM was higher in differentiating between normal and osteoporosis (P = 0.44), and between osteopenia and osteoporosis (P = 0.13), but without statistical significance. The AUC of QSM+PDFF was significantly higher than that of PDFF for differentiating between osteopenia and osteoporosis (0.82 vs. 0.70, P = 0.039). DATA CONCLUSION: The combination of vertebral susceptibility and fat content may be a promising marker for assessing postmenopausal osteoporosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1020-1028.

Insight into the roles of tyrosine on rCHO cell performance in fed-batch cultures.

Tyrosine (Tyr), as one of the least soluble amino acids, is essential to monoclonal antibody (mAb) production in recombinant Chinese hamster ovary (rCHO) cell cultures since its roles on maintaining the specific productivity (qmAb) and avoiding Tyr sequence variants. To understand the effects of Tyr on cell performance and its underlying mechanisms, rCHO cell-producing mAbs were cultivated at various cumulative Tyr addition concentrations (0.6 to 5.5 mM) in fed-batch processes. Low Tyr concentrations gave a much lower peak viable cell density (VCD) during the growth phase and also induced rapid cell death and pH decrease during the production phase, resulting in a low efficient fed-batch process. Autophagy was initiated following the inhibition of mTOR under the Tyr starvation condition. Excessive autophagy subsequently induced autophagic cell death, which was found as the major type of cell death in this study. Additionally, the results obtained here demonstrate that the decrease in culture pH under the Tyr starvation condition was associated with the autophagy and such pH drop might be attributed to the lysosome acidification and cell lysis.

Arthroscopic subscapularis augmentation combined with capsulolabral reconstruction is safe and reliable.

PURPOSE: The study aimed to compare modified arthroscopic subscapularis augmentation (MASA) with tenodesis of the upper third of the subscapularis tendon using a tendon combined with capsulolabral reconstruction (Group A) or Bankart repair (Group B) for recurrent anterior shoulder instability (RASI). METHODS: A retrospective series of 49 patients underwent primary surgery for RASI with glenoid bone loss (GBL) < 25%. Outcomes included the Oxford Shoulder Instability Score (OSIS), Visual Analogue Scale (VAS) score, Rowe score, and American Shoulder and Elbow Surgeons (ASES) functional outcome scale score. Recurrent instability, sports activity level, and range of motion (ROM) were also analysed. RESULTS: No significant differences were observed at baseline. Forty-six patients were available for more than 2 years of follow-up. At the last follow-up after surgery, the patients in both groups had experienced significant improvements in all outcome scores (P < 0.05 for all), and obvious decreases in forward flexion and external rotation were noted in both groups (P < 0.05 for all). Group A had superior ASES scores, VAS scores, and OSISs (P < 0.05) but did not experience significant differences in either the Rowe score or ROM compared to Group B. Group A had lower rates of recurrent instability and superior outcomes for the return to sports activities. One patient in Group A had subluxation, and 4 patients in Group B had dislocation or subluxation. No patients in either group experienced neurovascular injury, joint stiffness, or surgical wound infection. CONCLUSION: For RASI with GBL < 25%, MASA with tenodesis of the upper third of the subscapularis tendon using a tendon combined with capsulolabral reconstruction was a safe technique that produced better outcomes in terms of ASES scores, VAS scores, OSISs, the return to sports, and postoperative recurrent instability and did not decrease the ROM compared to that achieved by arthroscopic Bankart repair. LEVEL OF EVIDENCE: III.

[Establishment of Sampling Inspection Scheme Paradigm for Medical Device Sampling Inspection].

This paper introduces the sampling scheme and the inspection scheme paradigm followed in organizing the sampling inspection of medical devices. The sampling scheme paradigm includes the definition and operation guidelines for sampling products, the regulations for individual sampling batches and related model specifications, accessory data, validity period, storage conditions, etc., the requirements for sampling areas, places and quantities, and the requirements for samples to be sent to inspection institutions. The inspection scheme paradigm includes the provisions for inspection basis, inspection items and determination principles.