OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Gentianopsis barbata (G. barbata) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (1-50), including nine previously undescribed compounds (1, 2, 7, 10, 20, 28, 29, 37, and 41) were isolated and characterized from the whole plants of G. barbata. Notably, compounds 1 and 2 exhibited the novel 3,4;9,10-diseco-24-homo-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in G. barbata and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.
Triterpenes/isolation & purification* ; Mice ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Humans ; RAW 264.7 Cells ; Hep G2 Cells ; Interleukin-6/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Medicine, Mongolian Traditional ; Macrophages/immunology* ; Protective Agents/isolation & purification* ; Liver/drug effects* ; Gentianaceae/chemistry* ; Plant Extracts/chemistry* ; Molecular Structure

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Artificial intelligence (AI) is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention, such as machine learning; this technology is revolutionizing and reshaping medicine. AI has considerable potential to perfect health-care systems in areas such as diagnostics, risk analysis, health information administration, lifestyle supervision, and virtual health assistance. In terms of immunotherapy, AI has been applied to the prediction of immunotherapy responses based on immune signatures, medical imaging and histological analysis. These features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy, optimizing treatment planning, predicting outcomes of care and reducing human resource costs. In this review, we present the details of AI and the current progression and state of the art in employing AI for cancer immunotherapy. Furthermore, we discuss the challenges, opportunities and corresponding strategies in applying the technology for widespread clinical deployment. Finally, we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future.

Objective To explore the values of metrics on intravoxel incoherent motion (IVIM) and gadoxetic acid enhanced T1ρ imaging for staging of non?alcoholic fatty liver disease activity scores (NAS) and inflammation in nonalcoholic steatohepatitis (NASH) rabbits model. Methods NASH rabbits model was established by feeding with a varied duration (4, 8, 12 weeks) of high?fat, high?cholesterol diet. IVIM and gadolinium?ethoxybenzyl?diethylenetriamine pentaacetic acid (Gd?EOB?DTPA) enhanced T1ρ images were performed by a 3.0 T MR scanner. The inter?class correlation coefficients (ICC) and Bland?Altman analysis were applied to evaluate the reproducibility of the IVIM and Gd?EOB?DTPA enhanced T1ρ mapping measurers. Spearman correlation analysis were used to assess the correlation between MR metrics, including ADC, D, D*, f, T1ρ, T1ρ (hepatobiliary phase, HBP), and NAS score and inflammation grades respectively with reference to histopathology. ROC curve analysis was used to evaluate the diagnostic performance of T1ρ and IVIM parameters for NASH, inflammation grade, and hepatic fibrosis. Multiple linear regression equations were used to analyze the independent influence factors of T1ρ (HBP). Results The f value was negatively correlated with the NAS score (r=-0.530, P<0.01). The f value of the fibrosis S1?2 was significantly lower than that of the S0 (P<0.01). There was no statistical difference in D, D*, ADC among NASH score, inflammation, and fibrosis stage. T1ρ and T1ρ (HBP) values were positively correlated with NAS scores and inflammation grades. The area under curve (AUC) for the diagnosis of NASH for T1ρ, T1ρ(HBP), ADC, D, D*, and f values were 0.849, 0.949, 0.728, 0.596, 0.522, and 0.871, respectively. The AUCs of T1ρ (HBP)+f in the diagnosis of NASH, G2?3 inflammation, and F1?2 fibrosis were 0.971, 0.935, and 0.903, respectively. Fibrosis (R2=0.624, P=0.002) and inflammation (R2=0.746, P=0.002) were major independent factors of T1ρ (HBP). Conclusion Gd?EOB?DTPA enhanced T1ρ imaging can reflect the severity of NASH and degree of inflammation. IVIM measurements are not accurate enough to stage liver inflammatory activity of NASH. T1ρ (HBP)+f might be a superior noninvasive imaging biomarker than either non?enhanced T1ρ or IVIM for NASH activity and inflammation assessments.

Objective: To explore the values of metrics on intravoxel incoherent motion (IVIM) and gadoxetic acid enhanced T₁ρ imaging for staging of non-alcoholic fatty liver disease activity scores (NAS) and inflammation in nonalcoholic steatohepatitis (NASH) rabbits model. Methods: NASH rabbits model was established by feeding with a varied duration (4, 8, 12 weeks) of high-fat, high-cholesterol diet. IVIM and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced T₁ρ images were performed by a 3.0 T MR scanner. The inter-class correlation coefficients (ICC) and Bland-Altman analysis were applied to evaluate the reproducibility of the IVIM and Gd-EOB-DTPA enhanced T₁ρ mapping measurers. Spearman correlation analysis were used to assess the correlation between MR metrics, including ADC, D, D^*, f, T₁ρ, T₁ρ (hepatobiliary phase, HBP), and NAS score and inflammation grades respectively with reference to histopathology. ROC curve analysis was used to evaluate the diagnostic performance of T₁ρ and IVIM parameters for NASH, inflammation grade, and hepatic fibrosis. Multiple linear regression equations were used to analyze the independent influence factors of T₁ρ (HBP). Results: The f value was negatively correlated with the NAS score (r=-0.530, P<0.01). The f value of the fibrosis S1-2 was significantly lower than that of the S0 (P<0.01). There was no statistical difference in D, D^*, ADC among NASH score, inflammation, and fibrosis stage. T₁ρ and T₁ρ (HBP) values were positively correlated with NAS scores and inflammation grades. The area under curve (AUC) for the diagnosis of NASH for T₁ρ, T₁ρ(HBP), ADC, D, D^*, and f values were 0.849, 0.949, 0.728, 0.596, 0.522, and 0.871, respectively. The AUCs of T₁ρ (HBP)+f in the diagnosis of NASH, G2-3 inflammation, and F1-2 fibrosis were 0.971, 0.935, and 0.903, respectively. Fibrosis (R²=0.624, P=0.002) and inflammation (R²=0.746, P=0.002) were major independent factors of T₁ρ (HBP). Conclusion Gd-EOB-DTPA enhanced T₁ρ imaging can reflect the severity of NASH and degree of inflammation. IVIM measurements are not accurate enough to stage liver inflammatory activity of NASH. T₁ρ (HBP)+f might be a superior noninvasive imaging biomarker than either non-enhanced T₁ρ or IVIM for NASH activity and inflammation assessments.

OBJECTIVE： To investigate the effects of Kangfuxin liquid on repairing cartilage defect model of knee osteoarthritis （KOA） in rabbits and its mechanism. METHODS： Totally 72 male New Zealand rabbits were selected and randomly divided into model control group and Kangfuxin low-dose， medium-dose， high-dose groups， with 18 rabbits in each group. A cartilage defect model of the medial femoral condyle of the right knee joint in rabbits was established by drilling after anesthesia surgery. Then the rabbits in each group were given medicine via articular cavity immediately. Kangfuxin low-dose， middle-dose and high-dose groups were given 20％， 40％， 80％ Kangfuxin liquid； model control group was given constant volume of normal saline consecutively， 0.2 mL/kg， once every 3 days. At 4th， 8th， 12th week after medication， the wound repair of cartilage defect in rabbits was observed. Immediately after medication and at 4th， 8th， 12th week after medication， repaired tissue of cartilage defect in rabbits was scored histologically with Wakitani scoring standard under light microscope. At 12th week after medication， pathological changes of repaired tissue of cartilage defect in rabbits were observed by Masson staining. The levels of NO， SOD and LPO in joint fluid and PYD in urine of rabbits were detected by ELISA. RESULTS： At 4th， 8th， 12th week after medication， compared with model control group， cartilage defects in rabbits were repaired well in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with immediately after medication and model control group at same time point， histomorphological score of repairing cartilage defect of knee joint in rabbits decreased significantly in Kangfuxin low-dose， medium-dose and high-dose groups （P＜0.05）. At 12th week after medication， compared with model control group， the histopathology degree of cartilage defect of knee joint in rabbits was significantly alleviated in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with model control group， the levels of NO and LPO in joint fluid and PYD level in urine were decreased to different extent in Kangfuxin low-dose， medium-dose and high-dose groups， while SOD level was increased to different extent； at 12th week after medication， the difference of each index has statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Kangangxin liquid can significantly repair cartilage defect of KOA cartilage defect model rabbits， the mechanism of which may be associated with increasing the expression of SOD and mediating NO-inhibited chondrocyte apoptosis.

Objective To explore the clinical results of the arthroscopic acromioplasty in the rotator cuff repair.Methods Sixty-five patients (42 males and 23 females) to receive suture bridge repair under the arthroscopy between May 2012 and May 2014 were selected and randomly divided into an experimental group and a control group.The experimental group was given suture bridge repair with acromioplasty,while the control group underwent the suture bridge repair without acromioplasty.The time of operation was recorded.The range of motion (ROM) of the shoulder,the UCLA shoulder scoring system (ULCA) score,American orthopedic surgeon scoring system (ASES) score,the visual analogue scale (VAS) score and Constant score were observed 3 and 12 months after the operation.Results There were no significant differences in age,sex and the affected side between the two groups.Significant differences were found between the two groups in the duration of the operation (t=-18.5,P＜0.05).There were no significant differences in the ROM and the ULCA,ASES,VAS and constant scores of the shoulder 3 and 12 months after the operation.Conclusion No significant differences were found in the ROM and the shoulder function scoring between giving acromioplasty under the arthroscopy or not.However,the operation time of undergoing acromioplasty under the arthroscopy was longer.

Objective To investigate the MRI manifestations and diagnostic value of adenomatoid tumor (AT)of epididymis. Methods The MRI features of 5 patients with AT of epididymis were analyzed retrospectively,which were confirmed by histopathology,and some relevant medical literatures were reviewed.Results The epididymal tumor was manifested as moderate signal on T1 WI and T2 WI,similar to adjacent testicule,and as moderate signal with slightly high rim-enhancement on enhanced T1 WI in 4 cases.Secondary infarction and chronic granulomatous inflammation in 1 patient was found and presented unevenly moderate signal on T1 WI,slight hypointensity on T2 WI, hyperintensity on DWI and rim-enhancement on dynamic enhancement MRI.Few hydrocele was detected in all 5 patients.Conclusion AT of epididymis is a rare benign neoplasm with some characteristic MRI features which is helpful for the preoperative diagnosis.