[Visual rehabilitation treatment for a patient with hemifield slide after pituitary adenoma resection: a case report].

The patient is a 28-year-old male who presented with hemifield slide for 10 months following surgery for a large pituitary adenoma. A comprehensive ophthalmological examination and visual function tests were conducted, including best corrected visual acuity, visual field, stereopsis, accommodative convergence, Worth four-dot test, and prism cover test for quantifying strabismus, along with assessments using a depression scale and a visual function questionnaire. Rehabilitation plans included applying press-on prisms to correct vertical strabismus, binocular vision training, and saccadic training. After rehabilitation, the patient was able to maintain binocular single vision at near and intermediate distances, experienced improved visual comfort, and showed significant improvements in scores on the depression scale and visual function questionnaire.

[Comparison of two different intramedullary rods combined with Ilizarov external fixation and wrapped autologous iliac bone grafting for the treatment of congenital tibial pseudarthrosis in children].

Objective: To compare the initial clinical efficacy of extensible intramedullary rod fixation and Williams intramedullary rod fixation combined with Ilizarov external fixation and wrapped autologous iliac bone grafting in the treatment of congenital tibial pseudarthrosis in children. Methods: A retrospective analysis was conducted on the clinical data of 60 children with Crawford Ⅳtype congenital pseudarthrosis of the tibia treated with combined surgery at the Orthopedics Department of Hunan Children's Hospital from January 2013 to December 2020.According to different internal fixation methods,patients were divided into the extensible intramedullary rod group (30 cases) and the Williams intramedullary rod group (30 cases). There were 12 males and 18 females in the extendable intramedullary rod group, aged (33.6±6.3) months (range: 18 to 44 months), while there were 10 males and 20 females in the Williams intramedullary rod group, aged (47.8±8.6) months (range: 36 to 66 months). The anteroposterior and lateral views of tibia and fibula and the full length anteroposterior film of both lower limbs were examined to compare the clinical treatment effects of the two groups at 1-,3-,6-,9-, and 12-month after surgery. Independent sample t-test, χ2 test or Fisher exact test was used for inter group comparison. Results: Both groups of children underwent surgery successfully, with postoperative follow-up time greater than 2 years. The extensible intramedullary rod group was followed up for (49.5±6.4) months, while the Williams intramedullary rod group was followed up for (53.7±10.5) months. The initial bone healing time between the broken ends of the tibial pseudarthrosis was (5.1±0.8) months in the extensible intramedullary rod group and (5.0±0.6) months in the Williams intramedullary rod group. There was no statistically significant difference between the two groups (t=0.584, P=0.562). The initial postoperative bone healing rate of the extensible intramedullary rod group was 93.3% (28/30), while that of the Williams intramedullary rod group was 96.7% (29/30). There was no statistically significant difference between the groups (χ2=0.351 P=0.554).The postoperative fracture rate of the extensible intramedullary rod group was 20.0% (6/30), while that of the Williams intramedullary rod group was 16.7% (5/30);Six cases (20.0%) in the extensible intramedullary rod group had unequal limb lengths in both lower limbs after surgery, with a limb length difference of (2.5±1.4)cm (range: 1.5 to 5.2 cm). Eight cases (26.7%) in the Williams intramedullary rod group had a limb length difference of (2.8±1.4)cm (range: 1.8 to 6.0 cm);After surgery, there were 4 (13.3%) cases of proximal tibial valgus deformity in the extensible intramedullary rod group, with an valgus angle range of (12.5±4.9)° (range: 7 °to 18°), and 3 (10.0%) cases in the Williams intramedullary rod group, with an valgus angle of (15.0±6.0)° (range: 9°to 21°). There were 2 (6.7%) cases of ankle valgus deformity in the extensible intramedullary rod group, with an valgus angle of (11.5±4.9)° (range: 8 °to 15°), and 4 (13.3%) cases in the Williams intramedullary rod group, with an valgus angle of (14.8±6.2)° (range: 6 °to 20°). The postoperative activities of the knee and ankle joints in the extensible intramedullary rod group were normal and unrestricted, with 4 cases of extensible intramedullary rod displacement.In the Williams intramedullary rod group, there were 30 cases of postoperative ankle joint stiffness and no displacement of the fixation position of the intramedullary rod.There was no statistically significant difference in postoperative complications between the two groups of children (all P>0.05). Conclusions: The use of both extensible intramedullary rods and Williams intramedullary rods in the combined surgery for congenital tibial pseudarthrosis in children can achieve effective internal fixation results. The initial postoperative bone healing rate is high, and there is no difference in the incidence of postoperative complications between groups. Both internal fixation methods have their own advantages and disadvantages, and suitable internal fixation methods can be selected based on the characteristics of the patient.

[Mid-to-long term clinical outcomes and predictors after anterior cruciate ligament revision].

OBJECTIVE: To assess the mid-to-long term clinical outcomes after anterior cruciate ligament (ACL) revision surgery and to analyze their predictors. METHODS: The medical records of 235 patients undergoing ACL revision surgery between Jan. 2001 and Dec. 2015 at Department of Sports Medicine, Peking University Third Hospital were reviewed. Data were collected including demographic information, information related to revision surgery (time and cause of graft failure, date of revision surgery, surgical technique, combined injuries and management, etc.), as well as information related to primary ACL reconstruction (time, cause and mechanism of first-time ACL rupture, date of primary ACL reconstruction, surgical technique, combined injuries and management, etc.). Patients were followed up at least 2 years after revision surgery for clinical outcomes [Tegner score, Lysholm score, and International Knee Documentation Committee (IKDC) subjective knee score]. Post-revision surgeries on the involved knee and the contralateral knee joint were also documented. Multivariate regression model was used to analyze the predictors of clinical outcomes after ACL revision surgery. RESULTS: A total of 166 (70.63%) patients were followed up at a mean of (4.44±2.40) years (2.03-14.63 years). Clinical outcomes improved significantly at the last follow-up from pre-operative level, with the Lysholm, Tegner, and IKDC scores improving from 70.51±21.25, 3.39±1.77, 63.78±15.04 to 88.64±14.36, 4.67±1.739, 80.23±13.31 (P < 0.05), respectively. Three (1.81%) patients experienced infection while 39 (23.49%) patients underwent surgery after revision surgery during the follow-up. Compared with that those occurred during sports, graft failure that occurred during daily activities or due to surgical technical errors that led to poorer clinical outcomes, with the Lysholm, Tegner, and IKDC scores of 9.90 (95%CI: 1.49-18.31), 1.41 (95%CI: 0.10-2.72), 10.35 (95%CI: 0.17-20.54), and 8.53 (95%CI: 1.31-15.75), 1.28 (95%CI: 0.14-2.43), 9.39 (95%CI: 1.03-17.74) lower, respectively. Compared with antero-medial portal, transtibial technique for placement of the femoral bone tunnel showed poorer Lysholm scores of 11.18 (95%CI: 4.73-17.63, P=0.001). Concurrent repair of medial meniscus yielded higher IKDC scores of 11.06 (95%CI: 1.21-20.92, P=0.029) than those with intact medical meniscus. Other factors showed no significant effect. CONCLUSION: ACL revision surgery is able to restore knee stability and improve knee function. Graft failure caused by sports, concurrent repair of medical meniscus and antero-medial portal technique predicts better outcomes after revision surgery.

[The mid-term and long-term results of endovascular treatment of C/D aorto-iliac artery occlusive disease].

Objective: To evaluate the safety and efficacy of the endovascular treatment for Trans-Atlantic Society Consensus (TASC) C/D aorto-iliac artery occlusive disease in mid-term and long-term follow-up. Methods: A total of 172 patients diagnosed with TASC C/D aorto-iliac lesions who received endovascular treatment from Chinese PLA General Hospital from January 2008 to January 2018 were retrospectively analyzed. The cohort was separated into covered stent group (61 cases), bare stent group (88 cases) and composite stent group (23 cases). Primary endpoint was primary patency, and secondary endpoints were freedom from target lesion revascularization (TLR) rate, major amputation rate and all cause death rate. Results: There were no significant difference of peri-operational all cause death rate and complication rate among all the groups(all P>0.05). Kaplan-Meier was used to analyze the primary patency at 5 year, which were 82.1%, 78.3% and 71.9% in covered stent group, bare stent group and composite stent group (χ(2)=3.47, P>0.05) , and primary patency at 10 year were 68.7%, 52.6% and 58.1%, respectively (χ(2)=18.91, P<0.05) . Freedom from TLR at 5 year were 88.5%, 82.6% and 78.1% in covered stent group, bare stent group and composite stent group (χ(2)=2.93, P>0.05) , and freedom from TLR at 10 year were 74.1%, 70.6% and 65.9%, respectively (χ(2)=6.16, P>0.05) . Diabetes, smoking, TASC D lesions and bare stent were identified as predictors of restenosis by logistic regression analysis. Conclusions: These results suggest that endovacular treatment is safe and effective to complex TASC C/D aorto-iliac artery occlusive disease in mid-term and long-term follow-up. The application of covered stent might further improve the long-term patency.

[Brain protection strategy and effectivity in pulmonary thromboendarterectomy].

Objective: To summarize the experience and effectivity of brain protection in 25 patients who suffered from chronic thromboembolic pulmonary hypertension (CTEPH) and received pulmonary thromboendarterectomy (PTE) under deep hypothermic circulatory arrest. Methods: Retrospective analysis of 25 PTE surgeries in our center from December 2016 to August 2018. All cases were completed underdeep hypothermic circulatory arrest. Standard brain protections were strictly executed, including: balanced and controlled extracorporeal circulation cooling, cerebral oxygen saturation (rSO(2)) monitoring, strictly control of circulatory arrest time, and etc. The neurological adverse events during the perioperative period were recorded and statistically analyzed, and the intelligence level and cognitive function of the patients were evaluated by MMSE scale and MoCA scale before surgery and discharge. Results: All the 25 patients successfully completed the surgery, and 1 patient (4%) died of postoperative infection. The mean pulmonary arterial pressure decreased from (52.9±16.7) mmHg before surgery to (23.6±8.1) mmHg immediately after surgery (t=10.01, P<0.01), and(20.7±7.9) mmHg at 3 months follow-up (t=10.73, P<0.01). Pulmonary vascular resistance decreased from 975.4 (788.6-1 292.8) dyn·s·cm(-5) to 376.1 (283.6-565.5) dyn·s·cm(-5) (Z=5.34, P<0.01). Neurological complications occurred in 3 patients during the perioperative period, including 2 patients with hypoxic encephalopathy, and 1 patient with cerebral hemorrhage. All 3 patients fully recovered before discharge. Univariate analysis showed that the duration of rSO(2)<40% and the maximum decrease rate of rSO(2) from baseline were significantly correlated with postoperative neurological damage. Multivariate analysis showed only time of rSO(2)<40% was significantly correlated with postoperative neurological damage. There was no significant difference in MMSE and MoCA score before and after surgery (P>0.05). Conclusions: Adequate brain protection measures are essential to reduce the neurological complications of PTE surgery. Real-time intraoperative monitoring of rSO(2) and strict control of circulatory arrest time can further reduce the occurrence of neurological damage.

[Surgical technique and mid-and-long curative effect analysis of primary repair of chronic Achilles tendon rupture].

Objective: To examine the surgical method and clinical outcome of primary repair of chronic Achilles tendon rupture. Methods: From March 2012 to August 2017, clinical data of 35 consecutive patients with chronic Achilles tendon rupture who were treated with primary repair by the same doctor at Department of Sports Medicine, Peking University Third Hospital were retrospectively analyzed.There were 29 males and 6 females with age of (41.0±9.3)years(range:29-65 years), the follow-up period was (45.6±17.2) months(range:17-82 months). All the patients had unilateral tendon rupture with 22 cases on the left and 13 cases on the right.The preoperative and postoperative Visual Analogue Scale(VAS), American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score(AOFAS), the Victorian Institute of Sport Assessment-Achilles(VISA-A), the Achilles tendon Total Rupture Score(ATRS)and the Tegner Activity Score of patients were collected and compared by paired-t test. Results: Among 47 patients with chronic Achilles tendon rupture, 35 patients were followed up for (45.6 ± 17.2)months(range: 17-28 months). No serious postoperative complications such as infection or nerve damage and rerupture outcomes were reported. At the last follow-up,the VAS decreased from 1.0(2.0) (M(Q(R))) preoperative to 0.0(0.8)(Z=-3.586, P=0.00), AOFAS increased from 64.3±12.5 to 97.0±5.0(t=-14.359,P<0.001), VISA-A increased from 51.3± 9.8 to 87.8±18.0(t=- 17.656, P=0.00), Tegner increased from 0.9±0.3 to 4.6±1.7(t=- 12.524, P=0.00)and ATRS increased from 40.0±3.5 to 97.9±3.9(t=-64.133,P=0.00). Twenty-eight patients (80.0%) had returned to their preinjury activity levels, and 7 patients (20.0%) no longer participate in recreational sports. According to Arner-Lindholm curative effect evaluation criteria, 32 cases(91.4%)gained the excellent results, 1 case(2.9%) of good and 2 cases(5.7%) bad, and the percentage of the cases with the excellent or good results was 94.3%. All except 2 patients with bad results could perform a single-limb heel rise painlessly. Conclusions: Primary repair is an efficient approach for chronic Achilles tendon rupture. The mid-and-long curative effect is satisfactory and stable.Compared with other surgical techniques, operation is relatively simple and economical. The primary repair is considerably safe, with few serious complications such as infection or nerve damage and reruptures.

[Reconstruct abdominal aortic branch arteries totally by endovascular repair in complex aortic aneurysms: a single-centre experience].

OBJECTIVE: To report experiences and results of complex aortic aneurysms involving the visceral arteries treating by total endovascular repair. METHODS: Seventy cases of thoracoabdominal aortic lesions treating by total endovascular repair in Department of Vascular Surgery, People's Liberation Army General Hospital from January 2011 to December 2014 were retrospectively analyzed. There were 47 cases underwent chimney technique, 6 underwent sandwich technique, 15 underwent fenestration technique and 2 underwent branched stent grafts technique. RESULTS: The average follow-up time was 21 months, range from 3 to 47 months. Completion angiography showed that typeⅠ endoleak of chimney, sandwich, fenestration and branched stent grafts group were 9/47, 5/6, 2/15 and 0, respectively. While at 30-day typeⅠ endoleak reduced to 7/47, 2/6, 0 and 0. During follow-up, there were 3 target vessel stents occlusion in chimney group, the patency rate of target vessel stent was 95.1% (58/61). In sandwich, fenestration and branched stent grafts group, all the target vessel stents kept patent. CONCLUSION: In this study, chimney, sandwich, fenestration and branched stent grafts techniques show good short-term and midterm results, the long-term effects still need further studies.

[Drug coated balloon with paclitaxel for the treatment of symptomatic peripheral artery disease: early and midterm results].

OBJECTIVE: To evaluate the safety and efficacy of the drug coated balloon (DCB) with paclitaxel in patients with symptomatic peripheral artery disease (PAD). METHODS: The clinical data of 18 patients, who were diagnosed as PAD and treated with DCB from October 2013 to June 2014 in Department of Vascular Surgery, People's Liberation Army General Hospital, were retrospectively analyzed.Thirteen male and 5 female patients were in the series, the mean age of the patients was (65±7) years, and the Rutherford's categories were level 3 to 5. Patients were followed up at 3- and 6-month postoperative. The main efficacy end point were late lumen loss(LLL), rate of restenosis and clinically driven target lesion revascularization (TLR). Meanwhile, the clinical events were recorded. RESULTS: Mean lesion length, the percentage of total occlusions and the percentage of in-stent restenosis were (138±91) mm, 9/18 and 2/18, respectively. Rate of technical success was 18/18. At 6-month postoperative, LLL, rate of restenosis and TLR were (0.1±0.9) mm, 2/14 and 0, respectively. There was no deaths or no amputations. CONCLUSION: DCB with paclitaxel is safe in patients with PAD, and associated with reductions in LLL, restenosis and clinically driven TLR 6-month postoperative.

Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.

Gene expression changes in chicken NLRC5 signal pathway associated with in vitro avian leukosis virus subgroup J infection.

Nucleotide-binding oligomerization domain-like receptors (NLRs) play a key role in the innate immune response as pattern-recognition receptors. However, the role of NLRC5, which is a member of the NLR family, in NF-κB activation and MHC-I expression remains debatable. Infection with the J group avian leukosis virus (ALV-J) can result in immunosuppression and a subsequent increase in susceptibility to secondary infection. This results in huge economic losses to the poultry industry worldwide. Using quantitative real-time polymerase chain reaction (qRT-PCR), we investigated the mRNA expression levels of NLRC5 signal pathway-related genes in secondary chicken embryo fibroblasts 7 days after infection with ALV-J. The results indicated that, compared with the control groups, the expression levels of TLR7, MHC-I, and IL-18 increased significantly in the infected groups at 7 days post-infection (d.p.i.). The expression levels of NLRC5 and IL-6 were conspicuously downregulated at 7 d.p.i., but the expression levels of NF-κB, STAT1, and STAT3 were not significantly altered. These results suggest that NLRC5 and some genes involved in the NLRC5 pathway play a key role in antiviral immunity, typically the response to ALV-J infection. Moreover, MHC-I expression levels vary between different cell types.

USP4 promotes invasion of breast cancer cells via Relaxin/TGF-ß1/Smad2/MMP-9 signal.

OBJECTIVE: Ubiquitin-specific protease 4 (USP4) is a deubiquitinating enzyme with key roles in the regulation of TGF-ß1 signaling, suggesting its importance in tumorigenesis. However, the underlying mechanisms causing this are not entirely clear. In the present study, we investigated the effect of USP4 on invasion and tumorigenesis of breast cancer cells, and explored its mechanism. MATERIALS AND METHODS: Effects of USP4 overexpression or USP4 silencing by small interfering RNA (USP4 siRNA) on invasion of breast cancer MDA-MB-231 and T47D cells in vitro was detected. Using siRNAs and inhibitors to examine the USP4 signaling pathway. RESULTS: The migration and invasion assays showed that USP4 promotes human breast cancer cell migration and invasion by USP4 overexpression, and knockdown of USP4 by siRNA inhibits human breast cancer cell migration and invasion. Treatment with RLX siRNAs, TGF-ß1 siRNAs, Smad2 siRNAs or BB94 (MMPs inhibitor) to USP4-overexpressing breast cancer cells revealed that USP4- induced RLX via TGF-ß1 pathway promotes the cell migration and invasion. Further studies demonstrated that USP4-mediated TGF-ß1 activation not only enhances the phosphorylation of Smad2 through TGF-ß, but also directly upregulate matrix metalloproteinase (MMP)-9-mediated cell migration and invasion of breast cancer cells. CONCLUSIONS: Therapies targeting the USP4 inhibits invasion of breast cancer cells via Relaxin/TGF-ß1/Smad2/MMP-9 signal. These results indicate that USP4 is an attractive target for breast cancer therapy.

Differentiating origins of outflow tract ventricular arrhythmias: a comparison of three different electrocardiographic algorithms

Our objective is to evaluate the accuracy of three algorithms in differentiating the origins of outflow tract ventricular arrhythmias (OTVAs). This study involved 110 consecutive patients with OTVAs for whom a standard 12-lead surface electrocardiogram (ECG) showed typical left bundle branch block morphology with an inferior axis. All the ECG tracings were retrospectively analyzed using the following three recently published ECG algorithms: 1) the transitional zone (TZ) index, 2) the V2 transition ratio, and 3) V2 R wave duration and R/S wave amplitude indices. Considering all patients, the V2 transition ratio had the highest sensitivity (92.3%), while the R wave duration and R/S wave amplitude indices in V2 had the highest specificity (93.9%). The latter finding had a maximal area under the ROC curve of 0.925. In patients with left ventricular (LV) rotation, the V2 transition ratio had the highest sensitivity (94.1%), while the R wave duration and R/S wave amplitude indices in V2 had the highest specificity (87.5%). The former finding had a maximal area under the ROC curve of 0.892. All three published ECG algorithms are effective in differentiating the origin of OTVAs, while the V2 transition ratio, and the V2 R wave duration and R/S wave amplitude indices are the most sensitive and specific algorithms, respectively. Amongst all of the patients, the V2 R wave duration and R/S wave amplitude algorithm had the maximal area under the ROC curve, but in patients with LV rotation the V2 transition ratio algorithm had the maximum area under the ROC curve.

Orientation relationship between α-Fe precipitate and α-Al2O3 matrix in iron-implanted sapphire.

Fe ions were implanted into α-Al2O3 single crystals (sapphire) at room temperature and annealed in a reducing atmosphere. The orientation relationships (ORs) between α-Fe particles and sapphire matrix were investigated using transmission electron microscopy (TEM). All the α-Fe particles have the orientation relationship (OR) of (111)α-Fe||(0001)sapphire and [11¯0]α-Fe||[112¯0]sapphire with sapphire. This OR is predicted precisely by the coincidence of reciprocal lattice points (CRLP) method. The other OR of (110)α-Fe||(0001)sapphire and [111]α-Fe||[51¯4¯0]sapphire reported before is confirmed by the same method to be one of the secondary preferred orientation relationships in the α-Fe/sapphire system.

Regulation of autophagy by miR-30d impacts sensitivity of anaplastic thyroid carcinoma to cisplatin.

miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3' UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.

Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature.

Chronic inflammation is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC). The causes of inflammation in ESCC, however, are undefined. Dietary zinc (Zn)-deficiency (ZD) increases the risk of ESCC. We have previously shown that short-term ZD (6 weeks) in rats induces overexpression of the proinflammatory mediators S100a8 and S100a9 in the esophageal mucosa with accompanying esophageal epithelial hyperplasia. Here we report that prolonged ZD (21 weeks) in rats amplified this inflammation that when combined with non-carcinogenic low doses of the environmental carcinogen, N-nitrosomethylbenzylamine (NMBA) elicited a 66.7% (16/24) incidence of ESCC. With Zn-sufficiency, NMBA produced no cancers (0/21) (P<0.001). At tumor endpoint, the neoplastic ZD esophagus, as compared with Zn-sufficient esophagus, had an inflammatory gene signature with upregulation of numerous cancer-related inflammation genes (CXC and CC chemokines, chemokine receptors, cytokines and Cox-2) in addition to S100a8 and S100a9. This signature was already activated in the earlier dysplastic stage. Additionally, time-course bioinformatics analysis of expression profiles at tumor endpoint and before NMBA exposure revealed that this sustained inflammation was due to ZD rather than carcinogen exposure. Importantly, Zn replenishment reversed this inflammatory signature at both the dysplastic and neoplastic stages of ESCC development, and prevented cancer formation. Thus, the molecular definition of ZD-induced inflammation as a critical factor in ESCC development has important clinical implications with regard to development and prevention of this deadly disease.

Analysis of concentration fluctuations in gas dispersion around high-rise building for different incident wind directions.

This article presents experimental results that illustrate the unsteady characteristics of gas dispersion around a complex-shaped high-rise building for different incident wind directions. A series of wind tunnel experiments were conducted using a 1:30 scale model that represented the real structures under study. The objective of this paper is to study the behaviour of concentration fluctuations through transient analysis. Tracer gas was continuously released from a point source located at different positions, and a time series of fluctuating concentrations were recorded at a large number of points using fast flame ionization detectors. The experimental data were analysed to provide a comprehensive data set including variances and associated statistical quantities. Both the unsteady characteristics of the system and their potential practical impact are presented and discussed. Under crowd living conditions, the air pollutant exhausted from one household could probably re-enter into the neighbouring households, traveling with ambient airflow. Such pollutant dispersion process is defined as air cross-contamination in this study. The results indicate that the wind-induced cross-contamination around the studied type of high-rise building should not be overlooked, and the fluctuating concentrations should be paid attention to particularly during the evaluation of a potential contamination risk. This study can help deepen our understanding of the mechanisms of air cross-contamination, and will be useful for implementing optimization strategies to improve the built environments in metropolitan cities such as Hong Kong.

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells.

The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor κB (NF-κB) activation. On the other hand, we also found that the adriamycin-activated NF-κB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-κB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-κB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-κB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component.

Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer.

Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasis-suppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer.

Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree.

Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1, keratin 9, keratin 16, desmoglein 1 and plakoglobin. Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain-of-function mutation highlights the role of domain 2B in mediating filament assembly.