Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis.

Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila, we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects.

New insights on the association of weight loss with the reduction in carotid intima-media thickness among patients with obesity: an updated systematic review and meta-analysis.

OBJECTIVES: Carotid intima-media thickness (CIMT) is a noninvasive marker of atherosclerosis, a typical pathologic process underlying cardiovascular diseases (CVDs). It is essential to explore the relationships between weight loss and the reduction of CIMT. STUDY DESIGN: This was an updated systematic review and meta-analysis. METHODS: A systematic literature search was conducted to collect relevant clinical trials. The pooled results of meta-analyses were assessed by weighted mean difference (WMD) and the corresponding 95 % confidence interval (95% CI). RESULTS: Thirty-three articles involving 2273 participants were collected in this meta-analysis. Among all participants with obesity, the pooled mean of weight loss was -23.26 kg (95% CI: -27.71 to -18.81), and the pooled mean change of CIMT was -0.06 mm (95% CI: -0.08 to -0.04). Compared with Non-surgical interventions, Surgical ones could lead to much higher weight loss (Pbetween groups < 0.001). A more significant CIMT reduction was identified among Surgical intervention patients than among Non-surgical intervention participants (Pbetween groups < 0.001). CONCLUSIONS: Effective interventions, especially Surgical interventions, could reduce the weight of patients with obesity, followed by the decline of CIMT, which might further disturb atherosclerosis progression and lower CVD risk.

Burden and trends of iodine deficiency in Asia from 1990 to 2019.

OBJECTIVES: Understanding iodine deficiency (ID) burdens and trends in Asia can help guide effective intervention strategies. This study aims to report the incidence, prevalence, and disability-adjusted life years (DALYs) of ID in 48 Asian countries during the period 1990-2019. STUDY DESIGN: Data on ID were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and estimated by age, sex, geographical region, and sociodemographic index (SDI). METHODS: The estimated annual percentage change (EAPC) was calculated to evaluate the changing trend of age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and age-standardized DALYs rate (ASDR) related to ID during the period 1990-2019. RESULTS: In Asia, there were 126,983,965.8 cases with 5,466,213.1 new incidence and 1,765,995.5 DALYs of ID in 2019. Between 1999 and 2019, the EAPC in ASIR, ASPR and ASDR were -0.6 (95% confidence interval [CI], -0.8 to -0.4), -0.9 (95% CI, -1.2 to -0.7), and -1.6 (95% CI, -1.8 to -1.5), respectively. Malaysia charted the largest decrease in ASIR, ASPR, and ASDR (82.4%, 85.3%, and 80.9% separately), whereas the Philippines and Pakistan were the only two countries that witnessed an increase in ASIR and ASPR. ID burdens were more pronounced in women, countries located to the south of the Himalayas, and low-middle SDI regions. CONCLUSIONS: The incidence, prevalence, and DALYs of ID in Asia substantially decreased from 1990 to 2019. Women and low-middle SDI countries have relatively high ID burdens. Governments need to pay constant attention to the implementation and monitoring of universal salt iodization.

[The surgical classification and surgical strategy for en bloc resection of spine tumor].

En bloc resection of spine tumor is the essential treatment method for primary malignant spine tumor,primary aggressive spine tumor and solitary spine metastasis.It can achieve good local control and improve the prognosis.However,given the complex anatomic structure and major adjacent tissue and organ of the spine,en bloc resection of spine tumor remains the research hotspot in surgical treatment of spine tumor.On the basis of adequate surgical classification and surgical strategy,experienced surgical team for spine tumor can achieve good surgical margin while decreasing the morbidity of the en bloc resection of spine tumor.However,the details of surgical classification and surgical strategy require further study.

[Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis].

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

[Research progress in clinical application of three-dimensional reconstruction in orbital measurement].

The structure of orbit is complex and its function is critical. Quantitative determination of orbital volume is valuable to diagnosis and treatment of orbital diseases, but a standardized and reproducible orbital volume measurement method is still not available. Recently, with the development of three-dimensional reconstruction, many researchers gradually convert their insight into three-dimensional orbital measurement. This paper reviews the common methods of three-dimensional orbital measurement used by investigators, including some innovative ideas, and their clinical applications in order to make a comprehensive overview of the current orbital measurement technology, explore the possible improvement direction, and better serve the clinical.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study.

BACKGROUND: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented. PATIENTS AND METHODS: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed. RESULTS: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'. CONCLUSIONS: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.

[Orbital Rosai-Dorfman disease: a case report].

A 19-year-old patient with bilateral eyelid swelling for more than 2 years visited the Department of Ophthalmology. Physical examination disclosed a moderately active mass in the upper eyelid and lacrimal gland area in each eye. Orbital MRI showed that the lacrimal glands were significantly enlarged and moved forward in both eyes, and the enlargement was more severe in the left eye. The patient was admitted twice to the hospital for removal of orbital masses and was diagnosed as orbital Rosai-Dorfman disease by histopathological examination. During three months of follow-up, the patient was in good physical condition, and there was no tumor recurrence.

[Short-term efficacy and perioperative safety of catheter-based intervention for pulmonary vein stenosis caused by fibrosing mediastinitis].

Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. PATIENTS AND METHODS: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. RESULTS: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. CONCLUSION: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

Effects of probiotics on intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis by regulating Wnt/ß-catenin signaling pathway.

We aimed to explore the effects of probiotics on intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis, and to verify the Wnt/ß-catenin signaling pathway that regulates this process. A total of 30 SD rats were randomly divided into 3 groups, namely, control group (n=10), model group (n=10) and probiotic group (n=10). Rats in the model group were used to construct liver cirrhosis models using carbon tetrachloride (CCL4) method, and those in the probiotic group were administered with probiotic preparations by gavage for 8 weeks. Then the feces of rats in each group were taken to detect the composition of intestinal flora, and changes in the content of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and interferon-gamma (IFN-γ), in peripheral blood collected were examined by enzyme-linked immunosorbent assay (ELISA). Next, changes in the degree of liver cirrhosis were analyzed by hematoxylin and eosin (H&E) staining, and the expression levels of the Wnt/ß-catenin signaling pathway-related molecules, including ß-catenin, glycogen synthase kinase (GSK)-3ß and Frizzled-2, in liver tissues in each group were detected via polymerase chain reaction (PCR) and Western blotting (WB). Compared with rats in the control group, those in the model group had a disordered structure of hepatic lobule and hyperplasia of a large number of fibrous tissues. In contrast to those in the model group, the liver lobule structure was greatly improved, the edema cells were obviously reduced, and the hyperplasia of collagen fibers was remarkably alleviated in the probiotic group. Moreover, the degree of liver cirrhosis in the probiotic group was significantly reduced compared with that in the model group. Moreover, the rats in the model group exhibited a higher Bifidobacterium level in the intestinal tract, while those in the probiotic group displayed higher levels of microorganisms in the intestinal tract, such as Lachnospiraceae, Ruminococcaceae, Actinbacteria, Slackia and Pasteurellaceae. In comparison with that in the control group, the level of salt-tolerant Lactobacillus in the intestinal tract of rats in the model group was significantly decreased, while that in the probiotic group was partially increased (P=0.023). Meanwhile, some intestinal flora of rats in the control group, model group and probiotic group were closely correlated. Specifically, highly positive correlations were found between Bacteroidetes and Paraeggerthella (r=0.423, P=0.034) and between Firmicutes and Lactobacillus (r=0.318, P=0.027), but strongly negative associations were detected between Firmicutes and Paraeggerthella (r=-0.691, p=0.004) and between Paraeggerthella and Lactobacillus (r=-0.384, P=0.047). In addition, the levels of inflammatory cytokines TNF-α IL-6, MCP-1 and IFN-γ in the plasma of rats in the model group were markedly higher than those in the control group (P<0.05), whereas such levels in the probiotic group were decreased compared with those in the model group (P<0.05). PCR results revealed that the expression levels of ß-catenin and Frizzled-2 in the model group were higher than those in the control group, whereas they were lower in the probiotic group than those in the model group (P<0.05). Furthermore, the model group had a decreased level of GSK-3ß in comparison with the control group, but the probiotic group had a higher level of GSK-3ß than the model group (P<0.05). WB results were consistent with PCR results. Probiotics can affect intestinal flora, inflammation and degree of liver cirrhosis in rats with liver cirrhosis, and its mechanism may be related to the Wnt/ß-catenin signaling pathway.

Research progress into the physiological changes in metabolic pathways in waterfowl with hepatic steatosis.

1. When geese or ducks are overfed with a high-energy diet rich in carbohydrates, their liver increases in size by 5- to 10-fold in 2 weeks, which is accompanied by the occurrence of hepatic steatosis. As a result, this distinctive genetic characteristic of waterfowl has been taken advantage of to produce foie gras. 2. When overfed geese were fed a regular diet for a 20-d period of recovery, their liver was restored to the original state. Hence, the entire process is reversible, and cause no lasting cirrhosis or necrosis in the liver. This suggests that waterfowl have a mechanism to protect their liver from the harm caused by severe hepatic steatosis. 3. This paper reviews the formation, physiological changes to metabolic pathways and the protective mechanisms in geese and ducks with hepatic steatosis. Not only will understanding these mechanisms provide ideas for the waterfowl breeding selection for foie gras, it is conducive to improving production efficiency and quality of foie gras. This provides a scientific basis to ensure animal welfare and an approach to the prevention and treatment of fatty liver disease in human.

[Diagnostic performance of a novel Mycobacterium Tuberculosis specific T-Cell based assay for tuberculosis].

Objective: To evaluate the diagnosic performance of a novel Mycobacterium tuberculosis (MTB) specific T-cell based assay for tuberculosis, which targets the mRNA detection of interferon gamma-induced protein 10 (IP-10). Methods: Suspected tuberculosis patients were prospectively and consecutively recruited in Beijing Chest Hospital between March 2018 and November 2019, and individuals with lower risk of MTB infection were also recruited. IP-10.TB and T-SPOT.TB assays were simulataneously performed on peripheral blood samples. The diagnostic performance of IP-10.TB and T-SPOT.TB were analyzed using the receiver operating characteristic curve. Accordance of IP-10.TB and T-SPOT.TB was analyzed by Cohen's kappa test, while the correlation between the expression level of IP-10 mRNA in IP-10.TB test and the number of SFCs in T-SPOT.TB test were analyzed by Pearson correlation test. Results: A total of 235 patients with tuberculosis, 110 patients with other diseases and 153 individuals with lower risk of MTB infection were included in the final analysis. No significant difference was detected in the rate of indeterminate results between IP-10.TB assay (3/498, 0.60%) and T-SPOT.TB assay (6/498, 1.21%). The total sensitivity and specificity of IP-10.TB assay were 91.3% (95%CI 86.8%-94.6%) and 81.1% (95%CI 75.8%-85.7%). The specificity of IP-10.TB in individuals with lower risk of MTB infection was 98.0% (95%CI 94.4%-99.6%). The total sensitivity and specificity of T-SPOT.TB assay were 93.0% (95%CI 88.9%-96.0%) and 83.8% (95%CI 78.7%-88.1%). The specificity of T-SPOT.TB in individuals with lower risk of MTB infection was 100% (95%CI 97.6%-100.0%). No significant differences were detected in sensitivity and specificity between IP-10.TB and T-SPOT.TB assays (P>0.05). The positive coincidence rate of these 2 methods was 91.0% (95%CI 87.5%-94.5%), and the negative coincidence rate was 88.9% (95%CI 84.9%-92.9%) and the total coincidence rate was 90.0% (95%CI 87.3%-92.6%). The Cohen's kappa value was 0.80 (95%CI 0.75-0.85, P<0.001) between IP-10.TB and T-SPOT.TB assays. Conclusion: These results showed that the diagnostic performance of IP-10.TB was consistent with that in T-SPOT.TB, and this test could be a novel adjunctive tool for the diagnosis of tuberculosis.

[Comparison of biometric and structural ocular manifestations of Marfan syndrome in twins].

A pair of 16-year-old twin brothers presented to our hospital. The younger brother had been losing vision in his left eye for 6 months, and the older brother had been losing vision in both eyes for 6 months. Both patients were 2.05 meters tall and lean with spider-like fingers (toes). They had lens subluxation and a leopard-shaped fundus in both eyes. Their ocular manifestations, including anterior and posterior corneal curvature, total corneal refractive power, anterior and posterior and total corneal astigmatism, corneal thickness, and axial length, were relatively consistent. The twin brothers were both diagnosed with Marfan syndrome and bilateral lens subluxation, which is a relatively rare clinical condition. The younger brother underwent posterior scleral reinforcement for retinal foveoschisis in the left eye, and the retina was basically attached after surgery. The older brother was treated with optometry and frame glasses. (Chin J Ophthalmol, 2021, 57: 540-543).

Proteomics of Tear in Inactive Thyroid-Associated Ophthalmopathy.

Background: Thyroid-associated ophthalmopathy (TAO), one of the most common orbital diseases in adults, seriously reduces patients' quality of life. Although human tear proteomics identified many abnormal expressed proteins and proposed several pathogeneses of TAO, most of these studies focused on the active stage or mixed types in TAO. In this study we identified significantly changed proteins and preliminary revealed the potential signalling pathways and mechanisms of TAO with the late, inactive stage. Patients and Methods: Tears from TAO patients (n=6) with a CAS score < 3 and 6 control healthy subject were collected. The pooled tears were further fractionated using high pH reversed-phase chromatography, then submitted to LC-MS/MS and subsequent bioinformatic analysis. Results: Proteomic profiling identified 107 significantly changed proteins between the inactive stage of TAO patients and healthy cases. Among these proteins, 62 were upregulated, and 45 were downregulated in TAO cases compared to healthy individuals. Enrichment analysis revealed that the immune system, cell cycle, metabolism (carbohydrate metabolism and metabolism of cofactors and vitamins), protein synthesis and degradation might play a vital role in the progress of inactive TAO. The present investigation represents the first proteomic tear study of TAO patients in the inactive stage. Conclusion: The results shed light on the differences between inactive TAO patients and healthy cases, thus enabling us to understand better the molecular mechanisms and potential targets for the treatment of inactive TAO.

Predicting brain organization with a computational model: 50-year perspective on lateral inhibition and oscillatory gating by dendrodendritic synapses.

The first compartmental computer models of brain neurons using the Rall method predicted novel and unexpected dendrodendritic interactions between mitral and granule cells in the olfactory bulb. We review the models from a 50-year perspective on the work that has challenged, supported, and extended the original proposal that these interactions mediate both lateral inhibition and oscillatory activity, essential steps in the neural basis of olfactory processing and perception. We highlight strategies behind the neurophysiological experiments and the Rall methods that enhance the ability of detailed compartmental modeling to give counterintuitive predictions that lead to deeper insights into neural organization at the synaptic and circuit level. The application of these methods to mechanisms of neurogenesis and plasticity are exciting challenges for the future.

Immunologically modified MnFe2O4 nanoparticles to synergize photothermal therapy and immunotherapy for cancer treatment.

Immunotherapy has been a promising candidate for cancer treatment. The combination of photothermal therapy (PTT) and immunotherapy have shown to cause tumor ablation and induce host immune response. However, this strategy is often hampered by a limited immune response and undesirable immunosuppression. In this work, we developed an immunologically modified nanoplatform, using ovalbumin (OVA)-coated PEGylated MnFe2O4 nanoparticles (NPs) loaded with R837 immunoadjuvant (R837-OVA-PEG-MnFe2O4 NPs) to synergize PTT and immunotherapy for the treatment of breast cancer. The designed R837-OVA-PEG-MnFe2O4 NPs are able to elicit significant immune responses in vitro and in vivo. MnFe2O4 NPs also allowed for a reduction of systemic immunosuppression through downregulation of M2-associated cytokines. More importantly, the R837-OVA-PEG-MnFe2O4 NPs under laser irradiation effectively inhibited tumor growth and prevented lung metastases, leading to a prolonged survival time and improved survival rate. In addition, the designed multitasking MnFe2O4 NPs showed as a good contrast agent for magnetic resonance (MR) imaging to detect orthotopic breast tumor in vivo. Our work provides a novel strategy for combined PTT and improved immunotherapy in the treatment of breast and other metastatic cancers.

Porcine dermal collagen mesh (Permacol™) as a bioprosthesis in the ligation of intersphincteric tract (BioLIFT) procedure.

BACKGROUND: Ligation of intersphincteric tract (LIFT) is a sphincter-saving technique used to treat anal fistulas. Incorporation of a bioprosthesis in LIFT (BioLIFT) aims to improve healing. The use of cross-linked porcine dermal collagen mesh Permacol™ in BioLIFT has never been investigated. The aim of this study was to compare the healing rates and outcome of LIFT and BioLIFT for complex anal fistulas using the Permacol™ biological mesh. METHODS: A retrospective analysis of all patients having LIFT or BioLIFT for complex fistulas from January 2010 to November 2019 was performed in a tertiary referral centre. Patient data from a prospectively collected database of all patients having LIFT or BioLIFT were analyzed. RESULTS: LIFT and BioLIFT were performed in 48 (82.8%) and 10 (17.2%) patients, respectively. All BioLIFT patients had previous interventions for their fistulas compared to 30 (62.5%) of patients who had LIFT, p = 0.023. The primary healing rate for LIFT was 87.5% (42/48) compared to 80% (8/10) in BioLIFT, (p = 0.42). Eight (13.8%) patients developed complications, 6 (12.5%) in the LIFT group vs 2 (20%) in the BioLIFT group (p = 0.62). On univariate analysis, the number of previous operations was predictive of complications (p = 0.03). BioLIFT was not associated with complication (OR = 1.75, 95% CI: 0.30-10.3, p = 0.54) or primary healing (OR = 0.57, 95% CI: 0.97-3.36, p = 0.54). There was no significant difference in recurrence (LIFT 12.5% vs BioLIFT 0%, p = 0.58). Kaplan-Meier analysis found no difference in time to recurrence between the two groups (p = 0.65). CONCLUSION: Permacol™ mesh in BioLIFT is feasible and achieves a high primary healing rate of 80%. Prospective evidence is needed to establish the benefits of BioLIFT and determine whether Permacol™ is superior to the non-cross-linked porcine submucosal mesh.

[Expression and significance of Nek2B and ß-catenin in triple negative breast cancer].

Objective: To investigate the expression and significance of Nek2B and ß-catenin expression in triple negative breast cancer (TNBC) at molecule levels. Methods: By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and ß-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed. Results: Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/ß-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated ß-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and ß-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions: The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with ß-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/ß-catenin patients signaling pathway.

Linear polarization grating combining a circular polarization grating with a special cycloidal diffractive quarter waveplate.

We introduce and demonstrate a switchable novel linear polarization grating (LPG) consisting of a circular polarization grating (CPG) and a special cycloidal diffractive quarter waveplate (CQWP). The CQWP is developed that marvelously matches the polarization-state of beams passing through the CPG. Such an LPG is so polarization-sensitive that it can split an incident linear polarized beam into two proportionally controllable left- or right-handed circularly polarized lights. We establish rigorous simulation model based on finite element method to investigate near-field polarization-state distribution of CPGs. Furthermore, LPGs are demonstrated and the diffraction properties are obtained with simulation and Jones Matrix analysis. The combination of CPGs and CQWPs is achieved with polymerizable liquid crystal. The experimental results of deflection angle and polarization selectivity of LPGs are consistent with those of simulation.