TUC.338 promotes invasion and metastasis in colorectal cancer.

Ultraconserved regions (UCRs) are non-protein coding gene sequences that are strictly conserved across among different species. Emerging evidence demonstrates that transcribed ultraconserved regions (TUCRs) encoding noncoding RNAs serve as regulators of gene expression. In recent decades, increasing evidence implicates the involvement of UCRs in carcinogenesis. The role of TUC.338 in cervical cancers was an oncogene in previous studies. Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) markedly inhibited cell migration and invasion in SW480 and HCT116 colorectal cancer cell lines. TIMP-1 was demonstrated to be negatively regulated by TUC.338 at the posttranscriptional level, via a specific target site within the 3' untranslated region by dual-luciferase reporter assay. The expression of TIMP-1 was also observed to inversely correlate with TUC.338 expression in CRC tissues. Over-expression of TIMP-1 with migRI-TIMP-1-GFP inhibited CRC cell migration and invasion and down-regulates MMP9, resembling that of TUC.338-siRNA. Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion.

Investigation on the Interaction of Hydroxyethyl Starch 130/0.4 (Voluven) and Serum Albumin for Pharmacokinetic and Toxicological Implications.

The interaction of hydroxyethyl starch 130/0.4 (Voluven) with human serum albumin (HSA) has been investigated by fluorescence (steady state and synchronous), Fourier transforms infrared (FT-IR), and circular dichroism (CD) spectroscopies. Analysis of the fluorescence quenching data of HSA by Voluven using the Stern-Volmer method revealed the formation of 1:1 ground-state complex. Evaluation of binding parameters and binding energy indicated that the binding reaction was exothermic. On the basis of fluorescence measurements, it was concluded that electrostatic forces play a crucial role in stabilizing the complex. The binding distance was calculated by using Förster resonance energy transfer (FRET) theory. The conformational changes of HSA were obtained qualitatively as well as quantitatively using synchronous fluorescence, FT-IR, and CD. The HSA underwent partial unfolding in the presence of Voluven.

Shlnc-EC6 regulates murine erythroid enucleation by Rac1-PIP5K pathway.

Long noncoding RNAs (LncRNAs) are longer than 200 nucleotide noncoding RNAs without apparent functional coding capacity that function as regulators of cell growth and development. In recent years, increasing evidence implicates the involvement of LncRNAs in erythropoiesis. shlnc-EC6 is a LncRNA associated with erythroid differentiation but the mechanism remains undefined. In this study, we found that knockdown of shlnc-EC6 in purified mouse fetal liver erythroid progenitor and hematopoietic stem cells (FLEPHSCs) significantly blocked erythroid enucleation. We also showed that Rac1 was negatively regulated by shlnc-EC6 at the posttranscriptional level via specific binding to sites within the 3'UTR of Rac1 mRNA. Moreover, we found that knockdown of shlnc-EC6 led to upregulation of Rac1, followed by the activation of the downstream protein PIP5K, and subsequently resulted in the inhibition of enucleation in cultured mouse fetal erythroblasts. Thus, our findings suggest that shlnc-EC6 acts as a novel modulator to regulate mouse erythropoiesis via Rac1/PIP5K signaling pathway.

A minimally invasive medial patellofemoral ligament arthroscopic reconstruction.

The medial patellofemoral ligament reconstruction is recognized as a good choice for patients with recurrent patellar dislocation. Most techniques of the medial patellofemoral ligament reconstruction are open surgeries. Recently, we present a minimally invasive medial patellofemoral ligament arthroscopic reconstruction technique as a possible alternative method for recurrent patellar dislocation. The aim of the study was to describe a safe and effective technique to perform medial patellofemoral ligament reconstruction. The graft was prepared in shape to "Y." Two 5-mm incisions were made in the skin above the medial edge of the patella. Two docking bone tunnels were drilled from medial edge to the center of the patella, mimicking the wide patellar insertion of the medial patellofemoral ligament, and a bone tunnel was made at the femoral insertion site. Two free ends of the graft were fixed into the patellar tunnels by lateral cortical suspension, and the folded end was fixed into the femoral tunnel by bioabsorbable interference screw. Average patellar tilt and the congruence angle were 30.7° ± 7.5° and 52.7° ± 7.3° and were reduced to 12.8° ± 0.9° and 2.3° ± 11.5° after treatment. The Kujala score was increased from 63.0 ± 9.0 to 91.0 ± 7.0. The minimally invasive medial patellofemoral ligament arthroscopic reconstruction in this paper seems to be helpful to increase safe of operation and treatment effect and reduce complications.

Binding Analysis of Sf-SR-C MAM Domain and Sf-FGFR Ectodomain to Vip3Aa.

Bacillus thuringiensis Vip3Aa has been widely used in transgenic crops to resist the erosion of insects. The Scavenger Receptor-C (SR-C) and Fibroblast Growth Factor Receptor (FGFR) of Spodoptera frugiperda (Sf-SR-C and Sf-FGFR) have formerly been identified as the cell receptors of Vip3Aa. However, the interaction mechanism of Vip3Aa binding to Sf-SR-C or Sf-FGFR is still unknown. Here, we purified the MAM domain of Sf-SR-C (Sf-MAM) and the Sf-FGFR ectodomain expressed extracellularly by Sf9 cells. We then solved the crystal structure of the Sf-MAM domain. Structure docking analysis of the Sf-MAM and Vip3Aa C-terminal domain (CTD) excluded the possibility of the two proteins binding. A further surface plasmon resonance (SPR) assay also revealed that the Sf-MAM and Sf-FGFR ectodomain could not bind to the Vip3Aa protein. Our results have raised the urgency of determining the authentic cell receptor for Vip3Aa.

Structural insights into the Langya virus attachment glycoprotein.

Langya virus (LayV) was recently detected in patients with acute pneumonic diseases in China. Genome alignment indicated that LayV is a type of zoonotic henipavirus (HNV) that might also infect domestic animals. Previous studies revealed that HNVs mainly use ephrin-B1, ephrin-B2, or ephrin-B3 as cell receptors and the attachment glycoprotein (G) is the host cell receptor-binding protein. However, the LayV receptor remains unknown. Here, we present the 2.77 Å crystal structure of the LayV G C-terminal domain (CTD). We show that the LayV G protein CTD possesses a similar architecture as the Mojiang virus (MojV) G protein but is markedly different from the Nipah virus (NiV), Hendra virus (HeV), and Cedar virus (CedV) G proteins. Surface plasmon resonance (SPR) experiments indicate that LayV G does not bind ephrin-B proteins. Steric hindrance may prevent interactions between LayV G and ephrin-B. Our data might facilitate drug development targeting LayV.

Receptor binding mechanism and immune evasion capacity of SARS-CoV-2 BQ.1.1 lineage.

The global spread of COVID-19 remains a significant threat to human health. The SARS-CoV-2 BQ.1.1 lineage, including BA.5.2, BF.7, BQ.1 and BQ.1.1, caused a new soaring of infection cases due to rapid transmission. However, the receptor binding mechanism and immune evasion capacity of these variants need to be explored further. Our study found that while the BA.5.2, BF.7 and BQ.1.1 variants pseudovirus had similar cell entry efficiency, the BF.7 and BQ.1.1 RBD bound to human ACE2 (hACE2) with a slightly stronger affinity than the BA.5.2 RBD. Structural analysis revealed R346T, K444T, and N460K mutations altered RBD-hACE2 binding interface details and surface electrostatic potential of BQ.1.1 RBD. Serum neutralization tests showed BQ.1.1 variant had stronger immune evasion capacity than BA.5.2 and BF.7 variants. Our findings illustrated the receptor binding mechanism and serological neutralization activity of the BA.5.2, BF.7 and BQ.1.1 variants, which verified the necessity for further antibody therapy optimization and vaccination development.

Highly Optically Selective and Thermally Insulating Porous Calcium Silicate Composite SiO2 Aerogel Coating for Daytime Radiative Cooling.

Daytime radiative cooling technology offers a low-carbon, environmentally friendly, and nonpower-consuming approach to realize building energy conservation. It is important to design materials with high solar reflectivity and high infrared emissivity in atmospheric windows. Herein, a porous calcium silicate composite SiO2 aerogel water-borne coating with strong passive radiative cooling and high thermal insulation properties is proposed, which shows an exceptional solar reflectance of 94%, high sky window emissivity of 96%, and 0.0854 W/m·K thermal conductivity. On the SiO2/CaSiO3 radiative cooling coating (SiO2-CS-coating), a strategy is proposed to enhance the atmospheric window emissivity by lattice resonance, which is attributed to the eight-membered ring structure of porous calcium silicate, thereby increasing the atmospheric window emissivity. In the daytime test (solar irradiance 900W/m2, ambient temperature 43 °C, wind speed 0.53 m/s, humidity 25%), the temperature inside the box can achieve a cooling temperature of 13 °C lower than that of the environment, which is 30 °C, and the theoretical cooling power is 96 W/m2. Compared with the commercial white coating, SiO2-CS-coating can save 70 kW·h of electric energy in 1 month, and the energy consumption is reduced by 36%. The work provides a scalable, widely applicable radiative-cooling coating for building comfort, which can greatly reduce indoor temperatures and is suitable for building surfaces.

Medial retinaculum plasty versus medial patellofemoral ligament reconstruction for recurrent patellar instability in adults: a randomized controlled trial.

PURPOSE: The purpose of this study was to evaluate the clinical results of medial retinaculum plasty (MRP) and medial patellofemoral ligament reconstruction (MPFLR) with concomitant lateral retinacular release with respect to imaging and functional results. METHODS: Seventy patients with recurrent patellar instability were randomly divided into 2 groups based on their birth years (even/odd), receiving either MRP or MPFLR. Lateral retinacular release was also performed in all patients. Preoperatively, all patients received magnetic resonance imaging to evaluate the injury to the medial patellofemoral ligament. Computed tomography was performed before surgery and at follow-up. The subjective symptoms and functional outcome were evaluated preoperatively and postoperatively with the Kujala score, the Tegner activity score, and a subjective questionnaire. The physical apprehension test was examined, and redislocation was recorded. RESULTS: Patients were followed up for a mean period of 40 months (range, 24 to 55 months). The measurement results for the congruence angle, patellar tilt angle, and patellar lateral shift decreased significantly from the pretreatment measurements to the normal range at the latest follow-up, without a statistically significant difference between the 2 groups (P > .05). The median Kujala score had significantly improved after surgery. However, no statistically significant difference was found between the 2 groups at the latest follow-up (P > .05). In 6 cases in the MRP group (19%) and 3 in the MPFLR group (9%), we found patellar lateral shift that exceeded 1.5 cm but was less than 2.0 cm with a firm endpoint for the apprehension test, without a significant difference between the 2 groups. CONCLUSIONS: This prospective randomized study showed that MPFLR for recurrent patellar instability could achieve good clinical results, with a good congruous patellofemoral joint and good knee function. MRP could yield similar results to MPFLR for recurrent patellar instability in adults with medial patellofemoral ligament injuries from the patella or midsubstance portions. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Double-bundle anatomical versus single-bundle isometric medial patellofemoral ligament reconstruction for patellar dislocation.

PURPOSE: The purpose of this study was to evaluate reconstruction of the medial patellofemoral ligament (MPFL) using the double-bundle anatomical or single-bundle isometric procedure with respect to the patients' clinical outcomes. METHODS: In this retrospective study, we evaluated the clinical outcome of double-bundle anatomical versus single-bundle isometric reconstruction of the MPFL for patellar dislocation patients. Sixty-three patients were included in this study from August 2004 to January 2008. From August 2004 to September 2006, MPFL reconstruction using a single-bundle isometric technique was performed in 21 patients (26 knees). Since October 2006, the double-bundle anatomical reconstruction of the MPFL has been used as the routine surgical procedure. It was performed in 37 patients (44 knees). Fifty-eight patients (70 knees) could be followed up. According to the different techniques, we divided the patients into two groups: group D with double-bundle anatomical reconstruction (37 patients) and group S with single-bundle isometric reconstruction (21 patients). Clinical evaluation consisted of the number with a patellar re-dislocation, patellar apprehension sign, Kujala score, subjective questionnaire score, the patella lateral shift rate and patellar tilt angle measured by cross-sectional CT scan. RESULTS: According to the Kujala score and the subjective questionnaire score, the outcome of the double-bundle group was better than the outcome of the single-bundle group especially in the long-term. Patellar re-dislocation occurred in three patients in the group S, while no re-dislocation occurred in the group D. In total, 26.9 % of group S was considered to have patellar instability, compared to 4.54 % of the group D. After operation, the patellar tilt angle (PTA) and the patella lateral shift rate (PLSR) were restored to the normal range, with statistical significance (P < 0.05) compared to the preoperative state. CONCLUSION: Single- and double-bundle reconstruction of the MPFL can both effectively restore patella stability and improve knee function. However, outcomes in the follow-up period showed that the double-bundle surgery procedure was much better than in single-bundle surgery.

Effect of acute hypervolemic hemodilution with bicarbonated Ringer's solution on perioperative S100ß and NSE in elderly patients undergoing spine surgery.

To explore the effect of acute hypervolemic hemodilution (AHH) with bicarbonated Ringer's solution (BRS) on perioperative serum S100ß protein (S100ß) and neuron-specific enolase (NSE) in elderly patients undergoing spine surgery. Ninety patients with lumbar spondylolisthesis and fracture surgery admitted to our hospital from January 2022 to August 2022 were selected as the study subjects, and they were randomly and equally divided into group H1 (AHH with BRS), group H2 (AHH with lactated Ringer's solution) and group C (no hemodilution). The serum contents of S100ß and NSE of the three groups at different times were evaluated. There were significant differences in the incidence of postoperative cognitive dysfunction (POCD) among the three groups at T1 and T2 (P < 0.05). There were obvious differences in the contents of S100ß and NSE among the three groups at T1 and T2 (P < 0.001), with no overt difference in the incidence of perioperative complications among the three groups (P > 0.05). The use of AHH with BRS can effectively reduce the effect on cognitive function in the elderly with spine surgery, which greatly reduces the nervous system injury, and has certain application value in clinic.

Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression.

Background: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear. Purpose: To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338. Methods: UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study. Results: Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced. Conclusions: The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria.

Autophagy plays an important role in the interaction between viruses and host cells. SARS-CoV-2 infection can disrupt the autophagy process in target cells. However, the precise molecular mechanism is still unknown. In this study, we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes. From further investigation, we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy. The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy. Moreover, both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy, in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy. This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy, which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.

Two Resveratrol Oligomers Inhibit Cathepsin L Activity to Suppress SARS-CoV-2 Entry.

Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets. Molecular docking analysis suggested that the oligomers could occupy the active cavity of cathepsin L. The surface plasmon resonance assay showed that the equilibrium dissociation constant (KD) values of miyabenol C-cathepsin L and trans-ε-viniferin-cathepsin L were 5.54 and 8.54 µM, respectively, indicating their excellent binding ability for cathepsin L. Our study demonstrated the potential application of resveratrol oligomers as lead compounds in controlling SARS-CoV-2 infection by targeting cathepsin L.

Medial patellar retinaculum plasty versus medial capsule reefing for patellar dislocation in children and adolescents.

INTRODUCTION: The purpose of this study was to evaluate the clinical effect of medial patellar retinaculum plasty for children and adolescent patients with patellar dislocation. MATERIALS AND METHODS: A prospective study was performed between October 2005 and December 2009. Sixty-one cases of children and adolescent patients with patellar dislocation were admitted to our study. Twenty-nine patients received medial capsule reefing, of which 13 patients also received lateral retinacular release (LRR) (Group I). Thirty-two patients received medial patellar retinaculum plasty, of which 12 patients also received LRR (Group II). Preoperatively, all patients received magnetic resonance imaging (MRI) to evaluate the injury of medial patellofemoral ligament. And all patients received computed tomography (CT) scans on which the congruence angle (CA) and patellar lateral shift (PLS) could be evaluated with 30° knee flexion. Physical apprehension tests were examined and the redislocation was recorded. In addition, knee function was evaluated using the Kujala score and subjective questionnaires. RESULTS: Patients were followed up for a mean period of 50 months (25-75 months). For the comparison between the preoperative and postoperative results, the Kujala score improved significantly from 52.3 ± 2.9 to 78.1 ± 3.6 in Group I and from 53.5 ± 3.4 to 82.2 ± 3.4 in Group II (P < 0.05). There was significant difference of CA on CT scans and PLS with a statistical difference between the two groups (P < 0.05). Results of the apprehension test showed that nine patients had patellar lateral shift exceeding 1.5 cm with a soft end point in Group I and two patients had patellar lateral shift exceeding 1.5 cm with a hard end point in Group II (P < 0.05). Moreover, the subjective questionnaire revealed a significant difference of subjective effects between two groups (P < 0.05), including 7 excellent, 10 good and 12 fair in Group I and 18 excellent, 9 good, and 5 fair in Group II. CONCLUSION: The medial retinaculum plasty was better than medial capsule reefing in improving the subjective effects and decreasing the rate of patellar instability postoperatively in children and adolescent patients.

Land-Surface Diurnal Effects on the Asymmetric Structures of a Postlandfall Tropical Storm.

After a tropical storm makes landfall, its vortex interacts with the surrounding environment and the underlying surface. It is expected that diurnal variation over land will affect storm structures. However, this has not yet been explored in previous studies. In this paper, numerical simulation of postlandfall Tropical Storm Bill (2015) is conducted using a research version of the NCEP Hurricane Weather Research and Forecasting (HWRF) model. Results indicate that during the storm's interaction with midlatitude westerlies over the Great Plains, the simulated storm with the SLAB land-surface scheme is stronger, with faster eastward movement and attenuation, and more asymmetric structures than that with the NOAH land-surface scheme. More symmetric structures correspond with a slower weakening and slower eastward movement of the storm over land. Further diagnoses suggest an obvious response of the storm's asymmetric structures to diurnal effects over land. Surface diabatic heating in the storm environment is important for the storm's symmetric structures and intensity over land. Specifically, during the transition from nighttime to daytime, the evident strengthening of convective instability, atmospheric baroclinicity, and the lateral advection of high θ e air in the storm environment, associated with the rapid increase in surface diabatic heating, are conducive to the development of vertical vorticity and storm-relative helicity, thus contributing to the maintenance of the storm's symmetric structures and intensity after landfall.

Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis.

BACKGROUND: Cholestasis is a pathological condition involving obstruction of bile secretion and excretion that results in hepatotoxicity, inflammation, fibrosis, cirrhosis, and eventually liver failure. Common bile duct ligation (BDL) model is a well-established murine model to mimic cholestatic liver fibrosis. We previously reported that cytochrome P450 omega-hydroxylase 4a14 (Cyp4a14) plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)-related fibrosis. The goal of this study was to determine the role of Cyp4a14 in cholestatic-induced liver fibrosis. METHODS: C57BL/6 mice were subjected to BDL for 14 days, and Cyp4a14 mRNA and protein levels were examined and compared with those of the sham group. Cyp4a14 knockout mice and adeno-associated virus (AAV)-mediated overexpression of Cyp4a14 in C57BL/6 mice underwent BDL and liver histology, and key fibrosis markers were examined. RESULTS: Both hepatic Cyp4a14 mRNA and protein levels were markedly reduced in BDL liver compared with the time-matched sham group. Cyp4a14 gene-deficient mice aggravates whereas its overexpression alleviates BDL-induced hepatic fibrosis, which were determined by liver function, liver histology, and levels of key fibrotic markers including α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen 1a2 (Col1a2). CONCLUSION: Cyp4a14 exerts a contrasting role in different hepatic fibrosis models. Strategies that enhance Cyp4a14 activity may be potential strategies to cholestatic related liver fibrosis.

Esophageal carcinoma cell-excreted exosomal uc.189 promotes lymphatic metastasis.

Most cancers are old age-related diseases. Patients with lymphatic metastasis have an extremely poor prognosis in esophageal cancers (ECs). Previous studies showed ultraconserved RNAs are involved in tumorigenesis and ultraconserved RNA 189 (uc.189) served as an oncogene in cervical cancer, but the effect of exosomal uc.189 in esophageal squamous cell carcinoma (ESCC) remains undefined. This study revealed that uc.189 is closely correlated with lymph node (LN) metastasis and the number of lymphatic vessels in ESCC. ESCC-secreted exosomal uc.189 is transferred into human lymphatic endothelial cells (HLECs) to promote its proliferation, migration and tube formation to facilitate lymph node metastasis. Mechanistically, uc.189 regulated EPHA2 expression by directly binding to its 3'UTR region through dual-luciferase reporter assay. Over-expression and knockdown of EPHA2 could respectively rescue and simulate the effects induced by exosomal uc.189. Especially, the uc.189-EPHA2 axis activates the P38MAPK/VEGF-C pathway in HLECs. Finally, ESCC-secreted exosomal of uc.189 promotes HLECs sprouting in vitro, migration, and lymphangiogenesis. Thus, these findings suggested that exosomal uc.189 targets the EPHA2 of HLECs to promote lymphangiogenesis, and may represent a novel marker of diagnosis and treatment for ESCC patients in early stages.

Effects of etanercept and infliximab on bone metabolism indexes in patients with ankylosing spondylitis.

Effect of etanercept and infliximab on bone metabolism indexes in patients with ankylosing spondylitis (AS) were evaluated. The clinical data of 80 patients with ankylosing spondylitis admitted to Affiliated Hospital of Hebei University of Engineering from June 2015 to March 2016 were selected. There were 39 patients treated with Enbrel as Enbrel group and 41 patients treated with Infliximab as Infliximab group. The general data of the two groups of patients were collected and various indexes before and 12 and 24 weeks after treatment were recorded. Adverse reactions of the two groups of patients after treatment were recorded and the clinical efficacy of the drugs was evaluated. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in both groups decreased significantly before and 12 and 24 weeks after treatment (P<0.05), and 24 weeks after treatment showed a downward trend compared with 12 weeks (P<0.05). The ß-collagen special sequence (ß-CTX) level in the two groups was significantly lower after treatment than before (P<0.0001). The adverse reaction rate of Infliximab group (21.95%) was higher than that of Enbrel group (5.13%) (P>0.05). The morning stiffness time, BASDAI and BASFI indexes of the two groups of patients after treatment were significantly lower than those before treatment (P<0.0001). Schober test was significantly higher than that before treatment (P<0.0001); BASDAI in Infliximab group was lower than that in etanercept group (P<0.05). Both etanercept and infliximab have good therapeutic effects on AS, which can reduce the bone metabolism level of ß-CTX in AS patients and effectively improve the symptoms of affected medullary joints. The short-term efficacy of the two groups of patients is similar, but the incidence of adverse reactions of etanercept is slightly lower than that of infliximab.

Changes in Cartilage and Subchondral Bone of Femoral Trochlear Groove After Patellectomy in Growing Rabbits.

OBJECTIVE: To explore the effects of patellectomy on the bony and cartilaginous morphology of the trochlear groove in growing rabbits. METHODS: Forty-eight 4-week-old New Zealand white rabbits were randomly assigned to two groups. The control group underwent a sham surgical procedure, whereas the patellectomy group underwent patella excision surgery. Half of the rabbits in each group were sacrificed 3 months postoperatively; the rest were sacrificed 6 months postoperatively. Hematoxylin and eosin staining was performed on collected samples. Measurements included the bony and cartilaginous sulcus angles of the trochlear groove. In addition, the thickness of the articular cartilage at the deepest sulcus position (central thickness) and at the mid-position of the medial and lateral facets was measured and compared between groups. RESULTS: Three months after surgery, histological images revealed significant differences between the control group and the patellectomy group in cartilaginous sulcus angle (144.2° ± 1.5° vs 151.9° ± 2.4°, respectively; P < 0.001). No obvious difference in bony sulcus angle was found between the groups. Six months after surgery, significant between-group differences were observed in cartilaginous sulcus angle (136.3° ± 2.5° in control group vs 160.7° ± 3.0° in patellectomy group, P < 0.001) and bony sulcus angle (136.2° ± 2.2° in control group vs 160.4° ± 2.6° in patellectomy group, P < 0.001). However, there were no significant intra-group differences between cartilaginous and bony sulcus angles in either group. Three months after surgery, significant between-group differences were detected in articular cartilage thickness at the three different positions (medial facet: 324.3 ± 14.0 µm in control group vs 391.7 ± 98.8 µm in patellectomy group, P = 0.029; central position: 362.1 ± 13.6 µm in control group vs 730.3 ± 76.8 µm in patellectomy group, P < 0.001; lateral facet: 324.6 ± 12.7 µm in control group vs 358.5 ± 38.7 µm in patellectomy group, P = 0.009). No between-group differences in cartilage thickness were found at 6 months. CONCLUSIONS: Abnormal mechanical stress (patellectomy) during a rabbit's development can cause flattening of the femoral trochlear cartilage, followed by changes in the subchondral osseous layer. Abnormal mechanical stress is a crucial factor in the development of trochlear groove dysplasia.