Along with the popularity of youth movement, the incidence of osteochondritis dissecans (OCD) showed a trend of increase, but its pathogenesis is not yet clear. Previous studies suggested that trauma is the main potential cause, but with the emergence of vast family cases, hereditary factor is also gradually taken seriously. Arthroscopy is the "gold standard" for diagnosing OCD, but for the patient with early incomplete joint surface lesions, the diagnositic value of MRI is better than the arthroscopy. For the patients with stable form OCD, nonoperative management should be used such as adjusting activity, fixator and drugs; for the patient with unstable form OCD or failing after conservative treatment, surgery should be generally used such as joint clearing, drilling, microfracture method, fixation and transplantation. With the progress of research, stem cell technology and platelet-rich plasma gradually applied in cartilage repair, which will improve the curative effect of OCD, but still further clinical and experimental research, and also a long-term effective follow-up are needed.
Humans ; Osteochondritis Dissecans ; diagnosis ; etiology ; therapy

OBJECTIVETo evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).

METHODSThe efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.

RESULTSThe overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.

CONCLUSIONThe HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective To investigate the expression of microsomal glutathione S-transferase 1 ( MGST1) in hepa-tocellular carcinoma ( HCC) and its significance in the development of HCC. Methods Western blot was used to measure MGST1 expression in human hepatocellular carcinoma and adjacent tissues and HCC cell lines. Further-more, shRNA targeting MGST1 was constructed and transected into MHCC97H and HCCLM3 cells to deplete MGST1 expression. MGST1 was over-expressed in SK-Hep-1 cells using pCDH lentivirus system. Cell proliferation and migration were analyzed by colony formation and Transwell migration assay, respectively. The subcutaneous xenograft model of MHCC97H cells in nude mice was established to check tumor development and mouse survival.Results MGST1 was higher in 71% (17/24) of HCC tissues compared with their adjacent liver tissues. Cell proliferation and migration were significantly decreased by MGST1 knockdown, while they were increased by MGST1 overexpression. Furthermore, mice implanted with shMGST1 MHCC97H cells exhibited retarded tumor formation and tumor progression compared with control group. Conclusions MGST1 overexpression promotes hepatocellular carcinoma development and this molecule targeted for HCC treatment.

Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.

Objective: To explore the change rules of active ingredients in Phyllanthi Fructus of different storage years,in order to provide theory basis for storage. Method: Seven Phyllanthi Fruatus samples of different storage years were collected. HPLC-UV detection method was established to determine the contents of gallic acid,corilagin,chebulagic acid,ellagic acid and quercetin. Samples were fingerprinted by FT-NIR and identified by PLS-DA model. Result: Gallic acid,which was the bioactive marker in Chinese Pharmacopoeia,had the highest content. It was followed by ellagic acid and chebulagic acid,and corilagin and quercetin had the least content. The components had significant differences between samples of different storage years (P<0.05). Gallic acid and quercetin reached the maximum value at 6 years of storage,which were 79.36 and 1.68 mg·g^-1 respectively. The contents of chebulagic acid,corilagin and ellagic acid reached a maximum at 4 years of storage,which were 18.85,7.97,21.46 mg·g^-1,respectively. FT-NIR data was optimized by MSC+SG (second derivative, the window parameter as 11,and the polynomial order as 3). The classification accuracy was 84.5%. Spectral data reduced to several important potential variables,and was fused with 5 active components based on minimum cross-validation root mean square error,and the classification accuracy increased to 98.8%. Conclusion: The analysis of PLS-DA by HPLC-UV and FT-NIR could effectively explain the accumulation characteristics of active components in Phyllanthi Fruatus. According to the data fusion strategy,PLS-DA model could distinguish samples of different qualities. The results provide a scientific basis for the quality evaluation and identification of Phyllanthi Fruatus.

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.
4-Butyrolactone/chemistry* ; Animals ; Chromatography, Liquid ; Exosomes/chemistry* ; Hydroxybutyrates/chemistry* ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Oxybate/analysis* ; Tandem Mass Spectrometry/methods*

The aim of this paper was to investigate the flavonoids of callus of transgenic and non-transgenic Saussurea involucrate and its antitumor activity on the esophageal cancer CaEs-17 cells. The species and content of mono-phenols were detected by high performance liquid chromatography. The growth of human esophageal cancer CaEs-17 cells was detected using CCK-8 assay, apoptosis morphology observation and flow cytometry. Expression of related apoptotic genes Bax and Bcl-2 were determined by qPCR. The results showed that the content of total flavonoids in the transgenic callus was 2.72 times that of the non-transgenic callus. The cyanidin-galactoside was detected in the transgenic callus, but not in the non-transgenic callus. The inhibitory effect of the extracts from the transgenic callus on CaEs-17 cells was more significant than that of the non-transgenic callus, and the IC₅₀ value had a decreased of 26.4%. Flow cytometry analysis results showed that the apoptosis induction effect of the extracts from the transgenic callus on CaEs-17 cells was significantly better than that of the non-transgenic callus. Fluorescence quantitative PCR analysis results showed that the extracts from the transgenic callus could up-regulate the expression of proapoptotic gene Bax and down-regulate the expression of apoptotic gene Bcl-2, and the regulation effect of the transgenic callus was more significant. Therefore, compared with the non-transgenic callus, the antitumor activity of the extracts from the callus of transgenic S. involucrate on the esophageal cancer CaEs-17 cells was significantly increased, which was closely related to the accumulation of cyanidin-galactoside and its metabolism-related flavonoid compounds in the transgenic callus.
Apoptosis ; Chromatography, High Pressure Liquid ; Flavonoids ; Humans ; Phenols ; Plant Extracts ; Saussurea

Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
Animals ; Cell Line ; Cyclic AMP/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cytokines/metabolism* ; Humans ; Inflammation ; Macrophages ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Signal Transduction/drug effects* ; Taurochenodeoxycholic Acid/pharmacology*

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*