Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.

The incidence, clinical characteristics, and outcome of polytrauma patients with the combination of pulmonary contusion, flail chest and upper thoracic spinal injury.

BACKGROUND: Chest trauma was the third most common cause of death in polytrauma patients, accounting for 25% of all deaths from traumatic injury. Chest trauma involves in injury to the bony thorax, intrathoracic organs and thoracic medulla. This study aimed to investigate the incidence, clinical characteristics, and outcome of polytrauma patients with pulmonary contusion, flail chest and upper thoracic spinal injury. METHODS: Patients who met inclusion criteria were divided into groups: Pulmonary contusion group (PC); Pulmonary contusion and flail chest group (PC + FC); Pulmonary contusion and upper thoracic spinal cord injury group (PC + UTSCI); Thoracic trauma triad group (TTT): included patients with flail chest, pulmonary contusion and the upper thoracic spinal cord injury coexisted. Outcomes were determined, including 30-day mortality and 6-month mortality. RESULTS: A total 84 patients (2.0%) with TTT out of 4176 polytrauma patients presented to Tongji trauma center. There was no difference in mean ISS among PC + FC group, PC + UTSCI group and TTT group. Patients with TTT had a longer ICU stay (21.4 days vs. 7.5 and 6.2; p<0.01), relatively higher 30-day mortality (40.5% vs. 6.0% and 4.3%; p<0.01), and especially higher 6-month mortality (71.4% vs. 6.5%, 13.0%; p<0.01), compared to patients with PC + FC or with PC + UTSCI. The leading causes of death for patients with TTT were ARDS (44.1%) and pulmonary infection (26.5%) during first 30 days after admission. For those patients who died later than 30 days during the 6 months, the predominant underlying cause of death was MOF (53.8%). CONCLUSIONS: Lethal triad of thoracic trauma (LTTT) were described in this study, which consisting of pulmonary contusion,flail chest and the upper thoracic spine cord injury. Like the classic "lethal triad", there was a synergy between the factors when they coexist, resulting in especially high mortality rates. Polytrauma patients with LTTT were presented relatively high 30-day mortality and 6 months mortality. We should pay much more attention to the patients with LTTT for further minimizing complications and mortality.

Establishment of near-infrared on-line monitoring model and determination of endpoint in frying process of Hordei Fructus Germinatus / 中国中药杂志

Hordei Fructus Germinatus has been always used by "stir-frying" as a traditional medicine and the endpoint judgment of "fragrant" and "yellow" has been the focus and difficulty in frying process research. In this study, a quantitative calibration model between index components and NIRS was established in order to rapidly detect the contents of reducing sugar, total amino acids, total flavonoids, A420 and moisture; besides, an endpoint judgment method of frying process was put forward based on the "component change rate". Near-infrared spectra of samples with different frying time were collected, and a quantitative analysis model based on near-infrared spectroscopy was established to optimize the parameters such as spectral pretreatment and modeling band. HCA and PLS-DA were used to study the relationship between component and "stir-frying", and the endpoint of frying process was determined. The established calibration model had a good performance that the correlation coefficients between the predicted results and the actual measured values were both more than 0.9, with predicted relative deviations less than 10%. Hordei Fructus Germinatus with different frying time was divided into 4 categories by HCA analysis. PLS-DA analysis showed that total reducing sugar had a significant contribution to distinguishing the Hordei Fructus Germinatus of different frying time. When the change rate of total reducing sugar was 80%, it could judge that the endpoint of frying had been obtained. Results showed that NIRS could not only quickly and accurately determine the contents of reducing sugar, total amino acid, total flavonoid, A420 and moisture in Hordei Fructus Germinatus samples of different frying time, but also judge the endpoint of frying in the process. This study provided a new method for the evaluation and endpoint judgment of "stir-frying" process in research of traditional Chinese medicine.

Tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography: association with N categories.

OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.

Tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography: association with N categories

OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.

Dynamic change rules of active ingredients and inactive ingredients from Fructus Hordei Germinatus with frying process / 中国中药杂志

It is not scientific to explain that fried Fructus Hordei Germinatus is more effective than row Fructus Hordei Germinatus in resolving food stagnation from the aspects of amylase, tricine and other "active ingredients". In the present experiment, the contents of active ingredients including quercetin, tricine, kaempferol, catechin, ferulic acid and inactive ingredients including 5-hydroxymethyl furfural, acrylamide in frying process were determined by HPLC. The dynamic change rules of active ingredient and inactive ingredients in the frying process were investigated by HCA, PCA and PLS-DA analysis. The results showed that the Fructus Hordei Germinatus samples with different frying temperatures were classified into 4 groups by HCA and PCA analysis. PLS-DA analysis showed that frying temperature mainly impacted the contents of inactive ingredients including 5-hydroxymethyl furfural and acrylamide, with less effects on the contents of active ingredients. Simultaneously, with the increase of time in frying process, the content of 5-hydroxymethyl furfural was significantly increased from 2 min and became stable at 16 min, while the content of acrylamide was increased continuously from 18 min. Based on the variation of the contents of various ingredients, samples at different frying time were classified into 5 groups. The results showed that the content changes of "inactive ingredients" were closely related to the duration and degree of frying process, and the dynamic change rules of "inactive ingredients" can provide scientific basis for evaluating the frying process and elucidating the efficacy mechanism of Fructus Hordei Germinatus.