[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Facile dispersive solid-phase extraction based on humic acid for the determination of aflatoxins in various edible oils.

Aflatoxins (AFs), as the secondary metabolites of the toxigenic fungi Aspergillus flavus and Aspergillus parasiticus, are well known to be extremely harmful to humans and animals because of their high toxicity, mutagenicity, carcinogenicity, and teratogenicity. Recurring and increasing studies on AF ingestion incidents indicate that AF contamination is a serious food safety issue worldwide. Currently, immunoaffinity chromatography (IAC) has become the most conventional sample clean-up method for determining AFs in foodstuffs. However, the IAC method may be limited to some laboratories because it requires the use of expensive disposable cartridges and the IA procedure is time-consuming. Herein, to achieve the cost-effective determination of AFs in edible oils, we developed a dispersive solid-phase extraction (DSPE) clean-up method based on humic acids (HAs), which is followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. HAs could be directly used as a DSPE sorbent after simple treatment without any chemical modification. In the HA-DSPE, AFs could remain on the HA sorbent by both hydrophobic and hydrophilic interactions, whereas the oil matrix was retained on HA via only hydrophobic interactions. The oil matrix could be sufficiently washed off by n-hexane, whereas the AFs could still be retained on HA; thus, the selective extraction of AFs and clean-up of oil matrices were achieved. Under the optimal conditions of HA-DSPE, satisfactory recoveries ranging from 81.3% to 106.2% for four AFs (B1, B2, G1, and G2) were achieved in various oil matrices i.e. blended oil, mixed olive oil, tea oil, sunflower seed oil, rapeseed oil, sesame oil, soybean oil, rice oil, corn oil, and peanut oil. Minor matrix effects ranging from 89.3% to 112.9% were obtained for the four AFs, which were acceptable. Moreover, the LODs of AFs between 0.063 and 0.102 µg kg-1 completely meet the regulatory levels fixed by the Food and Drug Administration (FDA), the European Union (EU), China, or other countries. The proposed methodology was further validated using a naturally contaminated peanut oil, and the results indicated that the accuracy of the HA-DSPE could match the accuracy of the referenced IAC. In addition, HA-DSPE can be used to directly treat diluted edible oil without liquid-liquid extraction and HA is cheap and can be easily obtained from the market worldwide; these advantages make the proposed methodology simple, low-cost, and accessible for the determination of AFs in edible oils.

N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide promotes bone formation via the canonical Wnt/ß-catenin signaling pathway.

Osteoporosis is characterized by low bone mineral density and microarchitectural deterioration of bone tissue. N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (MBOC) is one of the macamides isolated from Maca (Lepidium meyenii Walp.), a cruciferous plant from the Andes of Peru. In this study, C3H/10T1/2 mesenchymal stem cells were treated with MBOC in osteogenic induction medium. An ovariectomized (OVX) mouse model was used to investigate the effect of 1-month MBOC treatment on the prevention of postmenopausal osteoporosis. Remarkably, trabecular thickness, trabecular number, and bone volume/tissue volume of the distal femoral metaphysis were significantly increased in OVX + MBOC mice compared with OVX mice, as revealed by microcomputed tomography analysis. Trabecular separation was decreased in OVX + MBOC mice compared with OVX mice. Consistently, MBOC increased the levels of osteocalcin and runt-related transcription factor 2 in OVX mice, as well as the expression of runt-related transcription factor 2, osterix, and alkaline phosphatase in C3H/10T1/2 cells. Mechanistically, MBOC activates the canonical Wnt/ß-catenin signaling pathway via inhibiting phosphorylation of GSK-3ß at Tyr216 and maintaining ß-catenin expression. Collectively, the current study demonstrates the robustness of MBOC in the induction of mesenchymal stem cells osteogenic differentiation and consequent bone formation, suggesting that MBOC may be a potentially effective drug to treat postmenopausal osteoporosis.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients.

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taixi (KI3), Fenglong (ST40), and Taichong (LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

Facile synthesis of magnetic carbon nitride nanosheets and its application in magnetic solid phase extraction for polycyclic aromatic hydrocarbons in edible oil samples.

In this study, we proposed a method to fabricate magnetic carbon nitride (CN) nanosheets by simple physical blending. Low-cost CN nanosheets prepared by urea possessed a highly π-conjugated structure; therefore the obtained composites were employed as magnetic solid-phase extraction (MSPE) sorbent for extraction of polycyclic aromatic hydrocarbons (PAHs) in edible oil samples. Moreover, sample pre-treatment time could be carried out within 10 min. Thus, a simple and cheap method for the analysis of PAHs in edible oil samples was established by coupling magnetic CN nanosheets-based MSPE with gas chromatography-mass spectrometry (GC/MS) analysis. Limits of quantitation (LOQs) for eight PAHs ranged from 0.4 to 0.9 ng/g. The intra- and inter-day relative standard deviations (RSDs) were less than 15.0%. The recoveries of PAHs for spiked soybean oil samples ranged from 91.0% to 124.1%, with RSDs of less than 10.2%. Taken together, the proposed method offers a simple and cost-effective option for the convenient analysis of PAHs in oil samples.

[Pharmaceutical research progress of rhynchophylla based on chemical stability].

Rhynchophylla is a Chinese herb commonly used in clinical practice. It's also the primary herb of some famous Chinese herbal compound such as Tianma Gouteng decoction, and Lingyang Gouteng decoction. According the record from many previous materia medica literatures, rhynchophylla should be added later during decoction. Pharmaceutical research showed that rhynchophylla alkaloids were not stable. Which has resulted in many problems in the research and its application. For example, there was not a quantitative determination method in "Chinese Pharmacopoeia" of past and present versions, which seriously impacted its quality control and product application. Firstly, records from previous materia medica literatures and "Chinese Pharmacopoeia" were systematically sorted based on the chemical stability of rhynchophylla. Secondly, pharmaceutical research including chemical compositions and their stability, pharmacological effects, extraction process and quality analysis, was reviewed after reference of literatures published at home and abroad in recent decades. Positive reference and evidence for further research and development of rhynchophylla will be provided in the article.

[Comparative study on rat in situ nasal absorption of geniposide of Xingnaojing nasal drop and Xingnaojing microemulsion].

Xingnaojing (XNJ) is an effective clinical drug used to treat acute stroke. Compared with injection administration, its nasal administration has better brain targeting. Therefore, through nasal administration, XNJ microemulsion could help solve the drug load of compound components of different polarities contained in large-dose and high-concentration traditional Chinese medicines, and reduce irritation to nasal mucosa In this study, the modified volume correction method and the improved rat in situ nasal perfusion model were adopted to compare the nasal absorption of geniposide contained in different XNJ preparations. The results showed that the constant absorption rate of geniposide (GE) in XNJ-D was (2.95 +/- 0.25) x 10(-3) min(-1), whereas the constant absorption rate of GE in XNJ-M was (2.16 +/- 0.21) x 10(-3) min(-1). This indicated that the rat nasal absorption of GE in different XNJ preparations complied with the first-order process and could be considered as passive absorption. GE in XNJ-D was absorbed faster than that in XNJ-M, which provided basis for the development of nasal preparations of XNJ.

Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.

BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 µM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Pure alumina bearings with cementless stems versus sandwich bearings with cemented stems in total hip arthroplasty.

BACKGROUND: Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years. METHODS: The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically. RESULTS: One ceramic liner fracture occurred in group A and five took place in group B (P < 0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P < 0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P < 0.05). Squeaking was not recorded in either group. CONCLUSIONS: The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.

Pure alumina bearings with cementless stems versus sandwich bearings with cemented stems in total hip arthroplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years.</p><p><b>METHODS</b>The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically.</p><p><b>RESULTS</b>One ceramic liner fracture occurred in group A and five took place in group B (P < 0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P < 0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P < 0.05). Squeaking was not recorded in either group.</p><p><b>CONCLUSIONS</b>The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.</p>

[Intermediate outcomes of alumina-on-alumina bearing total hip arthroplasty].

OBJECTIVE: To explore the intermediate outcomes of third-generation alumina-on-alumina total hip arthroplasty (THA). METHODS: A consecutive series of 165 primary alumina-on-alumina total hip arthroplasties were performed in 135 patients. Three patients died and 13 patients lost follow-up so that a total of 119 patients (146 hips) were available for study. The mean patient age was 53.4 ± 11.0 years old (range: 26 - 79). Hydroxyapatite. (HA)-coated press-fit acetabular cups were used in all cases. At femoral side, 123 cases were implanted with HA-coated uncemented stems and 23 cases implanted with high polished double taped cemented stems. All patients were evaluated clinically and radiographically after a minimal follow-up duration of 60 months. RESULTS: The preoperative mean Harris hip score of 49.6 ± 7.9 points improved to 91.7 ± 3.0 points at the last follow-up (P < 0.05). The 5-year survival for any reason lead to revision was 96.6%. Five hips were under revision, 1 for acetabular shell loosening and migration, 1 for Vancouver B2 periprosthetic fracture, 1 for fracture of pure alumina liner and 2 for infections. All other prostheses demonstrated no radiographic evidence of loosening. No periprosthetic osteolysis was found. There were 2 cases of dislocations and 2 patients presented postoperatively with "squeaking-like" hips. CONCLUSION: The clinical and radiographic outcomes after primary THA with third-generation ceramic-on-ceramic bearing surfaces are favorable after a minimal follow-up duration of 5 years. The modified alumina-on-alumina bearing implants offer a better option for younger and active patients.