Interleukin-17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression.

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.

The Safety and Efficacy of ZelanteDVT™ Catheter Rheolytic Thrombectomy in the Treatment of Patients with Iliac Vein Stent Thrombosis.

BACKGROUND: To examine the safety and efficacy of ZelanteDVT™ catheter rheolytic thrombectomy in the treatment of patients with iliac vein stent thrombosis. METHODS: A retrospective analysis method was conducted by means of collecting the data of 32 patients who had completed the treatment of iliac vein stent thrombosis with ZelanteDVT catheter rheolytic thrombectomy from March 2019 to March 2023. Data on clinical characteristics, technical success, clinical success, complications, and early follow-up were analyzed. RESULTS: The technical success rates were 100%, intraoperatively, in which 22 cases were improved to thrombus clearance Grade II (50-90%), 10 were Grade III (>90%). There were 21 cases treated with subsequent catheter-directed thrombolysis, and the average urokinase administration of (120.90 ± 29.63)∗10ˆ4 units. The clinical success rates were 100% and the swelling of the affected limbs were significantly improved, a significant difference in the pre/postoperative between-thigh circumference difference [(5.16 ± 1.08) vs. (1.75 ± 0.84), P < 0.000]. The pre/postoperative Venous Clinical Severity Score was [(12.94 ± 1.70) vs. (7.44 ± 1.31), P < 0.000]. No serious complications occurred during the perioperative period. The postoperative and 12-month stent patency rate was 100.00% (32/32) and 71.88% (23/32), respectively. CONCLUSIONS: The ZelanteDVT catheter rheolytic thrombectomy seems to have a promising application prospect for the treatment of patients with iliac vein stent thrombosis.

Analysis of canopy interception characteristics and influencing factors in typical artificial forest in the Loess Plateau semi-arid region.

Interception loss (IL) is an important process in the hydrological cycle within semi-arid forest ecosystems, directly affecting the amount of effective rainfall. However, the factors influencing IL during individual rainfall events remain to be quantified. This study collected rainfall, vegetation, and interception data during the 2022 and 2023 growing seasons in a typical black locust forest within the Zhifanggou watershed. It employed the Random Forest Regression (RFR) and back-propagation neural network (BPNN) methods to quantitatively evaluate the contribution rates of various factors to the IL and interception loss percentage (ILP). The IL among the 48 effective rainfall events was 172.05 mm, accounting for 19.54% of the rainfall amount. IL and ILP increased as the distance from the trunk decreased. During all rainfall events, both IL and ILP were significantly negatively correlated with the leaf area index (LAI) and canopy cover (CC); IL is significantly positively correlated with total rainfall (TR) and rainfall intensity (RI), while ILP is significantly negatively correlated with TR, RI, and rainfall duration (RD). The BPNN and RFR results indicated that rainfall, canopy, and tree characteristics contributed 43.06%, 44.79%, and 12.15% to IL, respectively, and 57.27%, 34.09%, and 8.63% to ILP, respectively. TR, CC, and LAI represented the primary influencing factors. Rainfall and canopy characteristics were the main factors affecting IL (ILP). As rainfall event magnitude increases, canopy contributions to IL and ILP decrease. In semi-arid areas, managing forest canopies to control IL helps address water imbalances in ecosystems.

Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.

BACKGROUND: At present, the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) is gemcitabine combined with cisplatin, but a considerable portion of ICC patients exhibit resistance to gemcitabine. Therefore, finding sensitisers for gemcitabine chemotherapy in ICC patients and predicting molecular markers for chemotherapy efficacy have become urgent needs. METHODS: In this study, PDX models were established to conduct gemcitabine susceptibility tests. The selected PDX tissues of the chemotherapy-sensitive group and drug-resistant group were subjected to transcriptome sequencing and protein chip technology to identify the key genes. Sixty-one ICC patients treated with gemcitabine chemotherapy were recruited for clinical follow-up validation. RESULTS: We found that thrombospondin-1 (TSP1) can predict gemcitabine chemosensitivity in ICC patients. The expression level of TSP1 could reflect the sensitivity of ICC patients to gemcitabine chemotherapy. Functional experiments further confirmed that TSP1 can increase the efficacy of gemcitabine chemotherapy for ICC. A mechanism study showed that TSP1 may affect the intake of oleic acid by binding to the CD36 receptor. CONCLUSIONS: In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study.

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

Mechanoredox/Nickel Co-Catalyzed Cross Electrophile Coupling of Benzotriazinones with Alkyl (Pseudo)halides.

An air-tolerant mechanoredox/nickel cocatalyzed cross electrophile coupling of benzotriazinones with alkyl (pseudo)halides is developed by liquid-assisting grinding in the presence of manganese powders and strontium titanate as a reductant and a cocatalyst, respectively. Mechanical activation of metal surfaces via ball milling eliminates the chemical activator for manganese, while mechanoredox cocatalysis of strontium titanate remarkably improves the aryl/alkyl cross electrophile coupling via piezoelectricity-mediated radical generation from alkyl halides. Both benzotriazinones and alkyl (pseudo)halides display reactivities in the mechanoredox/nickel cocatalysis different from those of conventional thermal chemistry in solution. The scope of the reaction is demonstrated with 26 examples, showing a high chemoselectivity of bromides vs chlorides.

The prevalence and risk factors of work related musculoskeletal disorders among electronics manufacturing workers: a cross-sectional analytical study in China.

OBJECTIVES: To describe the prevalence of self-reported musculoskeletal disorders among workers in the electronics manufacturing industry and to investigate the relations between work-related musculoskeletal disorders (WMSDs) and work-related variables. METHODS: An interview-based questionnaire survey was carried out in thirty electronics manufacturing factories in China in 2018. The prevalence of WMSDs was estimated using the modified Nordic Musculoskeletal Questionnaire (NMQ). A multivariate logistic regression model was applied to evaluate the effects of risk factors on WMSDs on multiple body parts. RESULTS: The 12-month prevalence of WMSDs among participants was 40.6%, and the common body sites affected were the neck (26.8%), shoulder (22.8%), upper back (14.9%), and lower back (14.8%). The results of logistic regression showed that female adults, > 5 job tenure and work-related factors (including awkward posture, lifting or carrying weights, excessive repetition, prolonged sitting, monotonous work and working under conditions of cold or temperature variations) led to a higher risk of WMSDs on most body parts. Upper back, wrist/hand and elbow pain levels were significantly higher for workers with vibration. However, more frequently, physical exercise was a protective factor against WMSDs on most body parts except the upper back, leg and knee. CONCLUSIONS: The study indicates a high prevalence of musculoskeletal pain among the electronics manufacturing industry in China. Different personal and work factors are related to the occurrence of WMSD on different body parts. Preventive measures should be implemented based on the characteristics of WMSD in the electronic manufacturing industry. Furthermore, the training and intervention guidance of ergonomic hazards in the workplace need to be strengthened by understanding the impact of bad posture, avoiding long-term sitting posture and increasing physical activities.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients.

BACKGROUND: Early singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features. METHODS: We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models. RESULTS: Our RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort. CONCLUSIONS: Compared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients' outcomes.

Comparative study on the clinical efficacy of small plate assisted anatomic plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of small plate assisted anatomical plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture. METHODS AND MATERIALS: The data of 68 patients with pilon fracture admitted to Hospital from June 2017 to June 2020 were retrospectively analyzed. Study group and control group were divided according to different operation methods, with 34 cases in each group. There were 28 cases of Rüedi and Allgöwer II type and 40 cases of Rüedi and Allgöwer III type. Perioperative period data, Ankle joint function score, visual analog scale (VAS) scores and the incidence of incision complications were analyzed between these two groups. RESULTS: There were no significant differences in full load time, fracture healing time between these two groups (P > 0.05). The operation time, intraoperative blood loss, length of hospital stay, Ankle joint function score and postoperative incision complication rate in observation group were lower than those in control group (P < 0.05). CONCLUSION: Small plate assisted anatomic plate is comparable to traditional double plate in the treatment of pilon fracture in terms of complete loading time, fracture healing time, but the former can shorten the operation time, reduce intraoperative blood loss and effectively reduce the incidence of postoperative complications.

HBV/Pregenomic RNA Increases the Stemness and Promotes the Development of HBV-Related HCC Through Reciprocal Regulation With Insulin-Like Growth Factor 2 mRNA-Binding Protein 3.

BACKGROUND AND AIMS: HBV-pgRNA (pregenomic RNA) has been proposed for predicting the response of nucleos(t)ide analogue (NA) treatment, guiding discontinuation of NA therapy and monitoring the emergence of viral mutations. However, the contributions of HBV-pgRNA to HCC remain open for study. APPROACH AND RESULTS: Double-center cohorts of serum samples with undetectable serum HBV-DNA (below the lower limit of detection) were obtained from long-term NA-treated (≥48 weeks) HBV-related HCC patients. The correlation between serum pgRNA concentration and the prognosis of HCC were analyzed. The role pgRNA played in HCC development was assessed both in vitro and in vivo. Our findings revealed that for patients who underwent long-term NA therapy with undetectable serum HBV-DNA, patients with high serum pgRNA expression had a poorer overall survival rate and higher cumulative recurrence rate after hepatectomy. Experiments demonstrated that pgRNA promotes proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, we found that pgRNA could up-regulate the expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a well-proven oncoprotein, at the posttranscriptional level. Furthermore, interferon (IFN)-α-2a could degrade the stability of pgRNA through increasing its N6-methyladenosine (m6A) RNA modification. Collectively, our findings uncover that serum pgRNA could serve as a potential biomarker for predicting the prognosis and recurrence of HCC in patients who received long-term NA therapy with undetectable serum HBV-DNA; and the pgRNA-IGF2BP3 axis plays an important role in the development of HBV-related HCC. Moreover, IFN-α-2a could reduce the stability of pgRNA by increasing its m6A RNA modification level, thereby suppressing the development of HBV-related HCC. CONCLUSIONS: In conclusion, our studies reveal a significance and mechanism of HBV-pgRNA in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HBV-related HCC.

Effects of endovascular treatment and prognostic factors for recovery of oculomotor nerve palsy caused by posterior communicating artery aneurysms: a multi-center retrospective analysis.

BACKGROUND: Oculomotor nerve palsy (ONP) may result from posterior communicating artery (PcomA) aneurysms. We aimed to evaluate the resolution of ONP after endovascular treatment with the intention of clarifying predictors of nerve recovery in a relatively large series. METHODS: A total of 211 patients with ONP caused by PcomA aneurysms underwent endovascular coiling between May 2010 and December 2020 in four tertiary hospitals. We evaluated the demographics, clinical characteristics, aneurysm morphology parameters and ONP resolution to analyze the predictors of ONP recovery using univariate and multivariate analyses. RESULTS: At the last available clinical follow-up, ONP resolution was complete in 126 (59.7%) patients, partial in 73 (34.6%) patients, and no recovery in 12 (5.7%) patients. The median resolution time after endovascular treatment was 55 days (interquartile range: 40-90 days). In multivariate analysis, degree of ONP (incomplete palsy) on admission (OR 5.396; 95% CI 2.836-10.266; P < 0.001), duration of ONP (≤ 14 days) before treatment (OR 5.940; 95% CI 2.724-12.954; P < 0.001) were statistically significant predictors of complete recovery of ONP. In the subgroup analysis of patients with unruptured aneurysms, aspirin showed a higher complete recovery rate in univariate analysis (OR 2.652; 95% CI 1.057-6.656; P = 0.038). CONCLUSION: Initial incomplete ONP and early management might predict better recovery of ONP after endovascular treatment.

Laparoscopic right hemihepatectomy following a novel optimized portal vein embolization: a video case report.

BACKGROUND: This article is the first report of laparoscopic major hepatectomy of Hepatocellular carcinoma (HCC) following optimized portal vein embolization (oPVE). CASE PRESENTATION: The patient was diagnosed with a single 3 × 3.5 cm HCC located in segment 5 and 8 detected by enhanced computed tomography and magnetic resonance imaging. The lesion was adjacent to the right anterior and posterior portal veins, making it difficult to confirm the adequate liver functional remnant volume, surgical margin and R0 resection. In addition, the liver cirrhosis induced by a long history of chronic hepatitis B virus increased the potential risk of postoperative liver failure and refractory ascites. Therefore, we conducted a laparoscopic surgery following oPVE, by which the safe tumor margin was ensured and the outcome of the surgery was improved. The patient was discharged on the seventh day after the surgery. The AFP gradually decreased to a normal level during the 90-day follow-up. CONCLUSION: This case report demonstrates that, in experienced hands for selected patients, laparoscopic hepatectomy after portal vein embolization is feasible and may be an alternative to open liver resection.

Relationship between annular calcification of plaques in the carotid sinus and perioperative hemodynamic disorder in carotid angioplasty and stenting.

OBJECTIVE: To investigate the correlation between annular plaque calcification in the carotid sinus and perioperative hemodynamic disorder (HD) in carotid angioplasty and stenting (CAS). METHODS: The clinical data of 49 patients undergoing CAS due to narrowing of the carotid sinus were retrospectively analyzed. All patients had preoperative carotid computed tomography angiography (CTA) and were divided into HD and non-HD groups based on the occurrence of HD in the perioperative period of CAS. HD was defined as persistent bradycardia (heart rate < 60 beats per min) or persistent hypotension (systolic blood pressure < 90 mmHg) in the perioperative period and lasting for at least 1 h. The baseline data, including the degree of carotid artery stenosis, plaque length, plaque thickness, calcified plaque morphologies (i.e., plaque circumferential angle: < 90° defined as dotted calcification; 90°-180° defined as arcuate calcification; > 180° defined as annular calcification), contralateral carotid artery conditions, balloon diameter, and stent types, were compared between the two groups. Binary logistic regression was used to analyze the risk factors for the occurrence of HD. RESULTS: Among the 49 patients undergoing CAS, 14 (28.57%) developed perioperative HD, and 35 did not. Annular calcification was more common in the patients in the HD group than in the non-HD group. No significant differences in the probabilities of dotted and arcuate calcifications were found between the two groups (p > 0.05). The duration of continuous dopamine consumption in the HD group was 9-71 h. The average hospital stay of the HD group (10.14 ± 4.17 days) was significantly longer than that of the non-HD group (6.57 ± 1.9 days; p < 0.001). Patients in the HD group had significantly more pronounced lumen stenosis (p = 0.033) and longer plaque length (p = 0.034) than those in the non-HD group. After adjusting for age and sex, multivariate regression analysis showed that the presence of annular plaque calcification was an independent predictor of HD (odds ratio: 7.68, 95% confidence interval: 1.46-40.37, p = 0.016). CONCLUSIONS: The occurrence of annular plaque calcification in the carotid sinus was an independent risk factor for perioperative HD in CAS. Preoperative carotid CTA assists with the early identification of high-risk patients who may develop HD.

lncRNA ZNF667-AS1 (NR_036521.1) inhibits the progression of colorectal cancer via regulating ANK2/JAK2 expression.

Long noncoding RNAs (lncRNAs) participate in many biological processes by affecting gene expression at the posttranscriptional level. lncRNAs are dysregulated in colorectal cancer (CRC) and this dysregulation is closely related to tumorigenesis, metastasis, and prognosis. Although many lncRNAs have been identified in CRC, the relation between ZNF667 antisense RNA 1 (head to head; ZNF667-AS1, accession: NR_036521.1) and CRC remains unclear. In this study, a total of 2,218 differentially expressed genes and 428 differentially expressed lncRNAs were identified between tumor and pericarcinous tissues. They were mainly enriched in cancer pathways, chemokine signaling, phosphoinositide 3-kinase-protein kinase B signaling pathway, and others. Key lncRNAs, including ZNF667-AS1, and their corresponding genes, such as ankyrin 2 (ANK2), were downregulated in CRC tumor tissues. In addition, downregulated ZNF667-AS1 (NR_036521.1) expression is associated with poor prognosis and disease progression. Overexpression of ZNF667-AS1 (NR_036521.1) inhibited the proliferation, migration, and invasion of VOLO cells both in vitro and in vivo. Moreover, Janus kinase 2 (JAK2) and ANK2 were significantly down- and upregulated in the overexpressed ZNF667-AS1 VOLO cells compared to those in the negative-control group. Knockdown of ANK2 or overexpression of JAK2 significantly counteracted the inhibitory effects of overexpression of ZNF667-AS1 on LOVO cell proliferation and migration. Taken together, it is indicated in our research that ZNF667-AS1 interaction with ANK2/JAK2 maybe important in CRC progression. Overexpression of ZNF667-AS1 could inhibit the proliferation, migration, and invasion of CRC cells, which may be related with the high ANK2 and low JAK2 levels.

Knockdown of Long Non-coding RNA LINC00473 Protects CHON-001 Cells against Interleukin-1ß-Induced Cell Injury.

Osteoarthritis (OA) is a chronic joint disease with high prevalence. However, effective treatment options for OA are still lacking. It was previously reported that LINC00473 was upregulated in patients with OA and upregulated LINC00473 might be associated with the progression of OA; however, the role of LINC00473 in OA remains to be investigated. CHON-001 human chondrocyte cells stimulated with 10 ng/mL interleukin (IL)-1ß were utilized to mimic OA in vitro. Protein expression, cell apoptosis and cell proliferation of CHON-001 cells were investigated by Western blot, Annexin V and propidium iodide (PI) double staining, cell counting-8 kit assay and immunofluorescence staining respectively. The result indicated IL-1ß triggered viability decrease and apoptosis in CHON-001 cells, which was alleviated by LINC00473 knockdown. Meanwhile, IL-1ß-induced upregulation of cleaved caspase 3 and Bax were ameliorated by LINC00473 knockdown. Likewise, IL-1ß-induced downregulation of X-linked inhibitor of apoptosis protein was alleviated by LINC00473 knockdown. In addition, LINC00473 knockdown protected CHON-001 cells against IL-1ß by inhibiting the methylation of LIM mineralization protein (LMP)-1 gene. Moreover, c-Jun N-terminal kinase (JNK)/nuclear factor-kappaB (NF-κB) signaling pathway was proved to be involved in the cell protective effect of LINC00473 knockdown in IL-1ß treated CHON-001 cells. Taken together, LINC00473 knockdown defended CHON-001 cells from IL-1ß induced cell injury via inhibition of the methylation of LMP-1. Thus, LINC00473 might possibly act as a novel therapeutic target for OA.

Comparison of Pharmacomechanical Catheter-Directed Thrombolysis versus Catheter-Directed Thrombolysis for the Treatment of Acute Iliofemoral Deep Vein Thrombosis: Measures of Long-Term Clinical Outcome and Quality of Life.

BACKGROUND: We studied the occurrence of post-thrombotic syndrome (PTS) in patients with either Pharmacomechanical Catheter-Directed Thrombolysis (hereafter "pharmacomechanical thrombolysis"; PT) or Catheter-Directed Thrombolysis (CDT) for the treatment of acute iliofemoral deep vein thrombosis (DVT). METHODS: This retrospective study of data archived between September 2013 and September 2015 was surveyed. Two separate patient populations were identified and analyzed: patients were separated into PT group or CDT group. For up to 5 years post-treatment, the incidence, severity of PTS, and chronic venous insufficiency questionnaire (CIVIQ) score difference were compared. RESULTS: The study identified 131 patients divided into PT group (65) and CDT group (66). Within the 5-year follow-up period, there was no significant difference in the incidence of PTS (45.0% PT vs. 57.6% CDT; odds ratio (OR) = 0.602; 95% confidence interval (CI), 0.291-1.242; P = 0.201), but there was reduced severe PTS in the PT group (Villalta scale ≥15 or ulcer:11.7% PT vs. 27.1% CDT; OR 0.355; 95%CI 0.134-0.941, P = 0.039; and Venous Clinical Severity Score (VCSS) ≥8: 13.3%PT vs. 28.8% CDT; OR 0.380; 95% CI 0.149-0.967, P = 0.045). There was also a larger improvement of venous disease-specific quality of life (QOL) in the PT group at 5 years [(62.89 ± 14.19) vs (56.39 ±15.62), P = 0.036] compared to the CDT group. CONCLUSION: In patients with acute iliofemoral DVT treated with PT, PT significantly reduced PTS severity scores, and resulted in greater improvement in venous disease-specific QOL. However, the incidence of was not significantly different from that measured in the CDT.

Efficacy and safety of raltitrexed-based transarterial chemoembolization for colorectal cancer liver metastases.

The liver is the most common site of colorectal cancer metastases. The present study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) with raltitrexed and oxaliplatin for colorectal liver metastases in a prospective, multicenter, single-arm trial conducted in 12 hospitals from different areas in China. A total of 90 patients with colorectal liver metastases were enrolled and treated by TACE with raltitrexed 4 mg and oxaliplatin 100 mg, followed by embolotherapy with 50 mg oxaliplatin and 5-20 ml lipiodol, administered every 28 days for four cycles. Patients were followed up every 3 months after the treatment and up to 12 months. The primary endpoint was time to progression. For the full analysis set (FAS), the median time to progression and overall survival were 9.1 and 17.8 months, respectively. The disease control rate in FAS was 71 (78.9%). Grade 3 or 4 adverse events were reported for 24 (26.7%) out of all 90 patients. Grade 3 thrombocytopenia, transglutaminase abnormality, and decreased neutrophil were observed in eight (8.9%), six (6.7%), and five (5.6%) patients, respectively. No unexpected adverse events or toxic deaths were observed. TACE with raltitrexed plus oxaliplatin is feasible, clinically beneficial, and well tolerated with low-grade toxicity for colorectal cancer patients with liver metastases.

2, 3, 5, 4'-Tetrahydroxystilbene-2-O-ß-D-glucoside prevention of lipopolysaccharide-induced depressive-like behaviors in mice involves neuroinflammation and oxido-nitrosative stress inhibition.

Although numerous hypotheses have been raised in recent years, the exact mechanisms that promote the development of major depression are largely unknown. Recently, strategies targeting the process of neuroinflammation and oxidative stress in depression have been attracting greater attention. 2, 3, 5, 4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), a compound purified from a traditional Chinese herbal medicine polygonummultiflorum, has been widely reported to inhibit neuroinflammation and oxidative stress. In this context, we investigated whether TSG affects lipopolysaccharide (LPS)-induced depressive-like behaviors in a manner associated with neuroinflammation and oxido-nitrosative stress. Results showed that administration of ICR mice with 0.83 mg/kg of LPS-induced typical depressive-like behaviors in the experiments of the tail-suspension test, the forced-swimming test, and sucrose preference, and these behaviors were prevented by TSG treatment (30 and 60 mg/kg). Further analysis showed that TSG pretreatment at the doses of 30 and 60 mg/kg not only inhibited the production of proinflammatory cytokines induced by LPS, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α, but also prevented the LPS-induced enhancement of oxido-nitrosative stress in mouse hippocampus and prefrontal cortex. The LPS-induced decreases in brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex were also prevented by TSG treatment. Generally, our data provide evidence to show that TSG could be used to cope with depressive-like symptoms by inhibition of neuroinflammation and oxido-nitrosative stress.

Effectiveness of catheter directed thrombolysis and stent implantation on iliofemoral vein thrombosis caused by iliac vein compression.

The purpose of this study was to objectively assess the morbidity of post-thrombotic syndrome (PTS) in iliofemoral vein thrombosis treated with catheter-directed thrombolysis (CDT) and stenting under the protection of inferior vena cava (IVC) filter. All patients with an unprovoked episode of iliofemoral vein thrombosis combined with iliac vein compression syndrome (IVCS) during January 2011 and January 2015 were enrolled. Clinical records of all patients were evaluated. Firstly, cox regression was performed to find out the factors impacted the incidence of PTS. Then, Kaplan Meier analysis was conducted to verify the roles of these factors in PTS. A total of 247 patients who underwent CDT and IVC filter insertion for iliofemoral vein thrombosis and were found stenosis in the iliac vein after CDT were included in this study. Among them, 74 patients suffered PTS diagnosed via Villalta scale. Comparison with patients without stent implantation and filter withdrawal, patients with stent implantation and filter withdrawal had a less risk of PTS, but patients with a lesion in the left or bilateral proximal deep vein had a more risk of PTS. Cox regression found that stent implantation was a preventive measure to prevent PTS (OR 0.541, 95% CI 0.334-0.876, p = 0.012). The Kaplan-Meier curve found that patients with stent implantation had a less ratio of PTS occurrence (P = 0.008). In patients with iliofemoral vein thrombosis and IVCS, stent implantation to solve the residual obstruction after CDT might play an important role in preventing PTS.

Ischemic Preconditioning protects hepatocytes from ischemia-reperfusion injury via TGR5-mediated anti-apoptosis.

Ischemic preconditioning (IP) has been shown to protect hepatic tissue from liver ischemia-reperfusion injury (IRI). TGR5, as a new-type bile acid receptor, has been shown protective roles in several liver diseases. However, the relationship between TGR5 and IP is still unknown. This study investigated effects of IP on TGR5 as well as the roles of TGR5 on hepatic tissue lesions and apoptosis in liver IRI. We showed that TGR5 was significantly upregulated in liver tissues after IP. To further analyzed effects of the TGR5 on liver IRI, wild type and TGR5 knockout mice were used to establish the liver IRI model. IP effectively alleviated liver IRI, but TGR5 deficiency significantly neutralized IP-related liver protection, as evidenced by serum alanine aminotransferase levels, histological liver damage, hepatocellular apoptosis and cytokines expressions. In addition, molecules related to apoptosis were detected by Western Blot, which showed that activation of TGR5 by IP increased expression of Bcl-2, and inhibited expressions of IRAK4 and cleaved caspase-3, but TGR5 deficiency abolished IP-induced expressions of anti-apoptosis molecule. In vitro, effects of TGR5 on hepatocytes were further analyzed by TGR5 agonist (INT-777) and hypoxia/reoxygenation (H/R), which displayed that INT-777 markedly attenuated H/R-induced hepatocellular apoptosis. In conclusion, our study indicates that IP alleviates hepatocellular apoptosis, and reduces liver IRI through TGR5-mediated anti-apoptosis functions.