Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study.

BACKGROUND: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. METHODS: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. RESULTS: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10-2, 1.7 × 10-2, respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10-4, 9.5 × 10-4, respectively). CONCLUSION: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted.

Investigation of the Photocatalytic Performance, Mechanism, and Degradation Pathways of Rhodamine B with Bi2O3 Microrods under Visible-Light Irradiation.

In the present work, the photodegradation of Rhodamine B with different pH values by using Bi2O3 microrods under visible-light irradiation was studied in terms of the dye degradation efficiency, active species, degradation mechanism, and degradation pathway. X-ray diffractometry, polarized optical microscopy, scanning electron microscopy, fluorescence spectrophotometry, diffuse reflectance spectra, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, UV-visible spectrophotometry, total organic carbon, and liquid chromatography-mass spectroscopy analysis techniques were used to analyze the crystal structure, morphology, surface structures, band gap values, catalytic performance, and mechanistic pathway. The photoluminescence spectra and diffuse reflectance spectrum (the band gap values of the Bi2O3 microrods are 2.79 eV) reveals that the absorption spectrum extended to the visible region, which resulted in a high separation and low recombination rate of electron-hole pairs. The photodegradation results of Bi2O3 clearly indicated that Rhodamine B dye had removal efficiencies of about 97.2%, 90.6%, and 50.2% within 120 min at the pH values of 3.0, 5.0, and 7.0, respectively. In addition, the mineralization of RhB was evaluated by measuring the effect of Bi2O3 on chemical oxygen demand and total organic carbon at the pH value of 3.0. At the same time, quenching experiments were carried out to understand the core reaction species involved in the photodegradation of Rhodamine B solution at different pH values. The results of X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffractometer analysis of pre- and post-Bi2O3 degradation showed that BiOCl was formed on the surface of Bi2O3, and a BiOCl/Bi2O3 heterojunction was formed after acid photocatalytic degradation. Furthermore, the catalytic degradation of active substances and the possible mechanism of the photocatalytic degradation of Rhodamine B over Bi2O3 at different pH values were analyzed based on the results of X-ray diffractometry, radical capture, Fourier-transform infrared spectroscopy, total organic carbon analysis, and X-ray photoelectron spectroscopy. The degradation intermediates of Rhodamine B with the Bi2O3 photocatalyst in visible light were also identified with the assistance of liquid chromatography-mass spectroscopy.

Association of fat mass and fat-free mass with all-cause and cause-specific mortality in Asian individuals: A prospective cohort study.

OBJECTIVE: The study's objective was to investigate the association of fat mass index (FMI) and fat-free mass index (FFMI) with all-cause mortality and cause-specific mortality in the Chinese population. METHODS: A total of 422,430 participants (48.1% men and 51.9% women) from the Taiwan MJ Cohort with an average follow-up of 9 years were included. RESULTS: The lowest (Q1) and highest (Q5) quintiles of FMI and FFMI were associated with increased all-cause mortality. Compared with those in the third quintile (Q3) group of FMI, participants in Q1 and Q5 groups of FMI had hazard ratios and 95% CI of 1.32 (1.24-1.40) and 1.13 (1.06-1.20), respectively. Similarly, compared with those in Q3 group of FFMI, people in Q1 and Q5 groups of FFMI had hazard ratios of 1.14 (1.06-1.23) and 1.16 (1.10-1.23), respectively. In the restricted cubic spline models, both FMI and FFMI showed a J-shaped association with all-cause mortality. People in Q5 group of FFMI had a hazard ratio of 0.72 (0.58-0.89) for respiratory disease. CONCLUSIONS: The mortality risk increases in those with excessively high or low FMI and FFMI, yet the associations between FMI, FFMI, and the risk of death varied across subgroups and causes of death.

6-Year trajectory of fasting plasma glucose (FPG) and mortality risk among individuals with normal FPG at baseline: a prospective cohort study.

BACKGROUND: Higher fasting plasma glucose (FPG) levels were associated with an increased risk of all-cause mortality; however, the associations between long-term FPG trajectory groups and mortality were unclear, especially among individuals with a normal FPG level at the beginning. The aims of this study were to examine the associations of FPG trajectories with the risk of mortality and identify modifiable lifestyle factors related to these trajectories. METHODS: We enrolled 50,919 individuals aged ≥ 20 years old, who were free of diabetes at baseline, in the prospective MJ cohort. All participants completed at least four FPG measurements within 6 years after enrollment and were followed until December 2011. FPG trajectories were identified by group-based trajectory modeling. We used Cox proportional hazards models to examine the associations of FPG trajectories with mortality, adjusting for age, sex, marital status, education level, occupation, smoking, drinking, physical activity, body mass index, baseline FPG, hypertension, dyslipidemia, cardiovascular disease or stroke, and cancer. Associations between baseline lifestyle factors and FPG trajectories were evaluated using multinomial logistic regression. RESULTS: We identified three FPG trajectories as stable (n = 32,481), low-increasing (n = 17,164), and high-increasing (n = 1274). Compared to the stable group, both the low-increasing and high-increasing groups had higher risks of all-cause mortality (hazard ratio (HR) = 1.18 (95% CI 0.99-1.40) and 1.52 (95% CI 1.09-2.13), respectively), especially among those with hypertension. Compared to participants with 0 to 1 healthy lifestyle factor, those with 6 healthy lifestyle factors were more likely to be in the stable group (ORlow-increasing = 0.61, 95% CI 0.51-0.73; ORhigh-increasing = 0.20, 95% CI 0.13-0.32). CONCLUSIONS: Individuals with longitudinally increasing FPG had a higher risk of mortality even if they had a normal FPG at baseline. Adopting healthy lifestyles may prevent individuals from transitioning into increasing trajectories.

Deep multi-task learning for nephropathy diagnosis on immunofluorescence images.

BACKGROUND AND OBJECTIVE: As an advanced technique, immunofluorescence (IF) is one of the most widely-used medical image for nephropathy diagnosis, due to its ease of acquisition with low cost. In practice, the clinically collected IF images are commonly corrupted by blurs at different degrees, mainly because of the inaccurate focus at the acquisition stage. Although deep neural network (DNN) methods achieve the great success in nephropathy diagnosis, their performance dramatically drops over the blurred IF images. This significantly limits the potential of leveraging the advanced DNN techniques in real-world nephropathy diagnosis scenarios. METHODS: This paper first establishes two IF databases with synthetic blurs (IFVB) and real-world blurs (Real-IF) for nephropathy diagnosis, respectively, including 1,659 patients and 6,521 IF images with various degrees of blurs. According to the analysis on these two databases, we propose a deep hierarchical multi-task learning based nephropathy diagnosis (DeepMT-ND) method to bridge the gap between the low-level vision and high-level medical tasks. Specifically, DeepMT-ND simultaneously handles the main task of automatic nephropathy diagnosis, as well as the auxiliary tasks of image quality assessment (IQA) and de-blurring. RESULTS: Extensive experiments show the superiority of our DeepMT-ND in terms of diagnosis accuracy and generalization ability. For instance, our method performs better than nephrologists with at least 15.4% and 6.5% accuracy improvements in IFVB and Real-IF, respectively. Meanwhile, our method also achieves comparable performance in two auxiliary tasks of IQA and de-blurring on blurred IF images. CONCLUSIONS: In this paper, we propose a new DeepMT-ND method for nephropathy diagnosis on blurred IF images. The proposed hierarchical multi-task learning framework provides the new scope to narrow the gap between the low-level vision and high-level medical tasks, and will contribute to nephropathy diagnosis in clinical scenarios. The diagnosis accuracy and generalization ability of DeepMT-ND are experimentally verified to be effective over both synthetic and real-world databases.

Prediction of risk and overall survival of pancreatic cancer from blood soluble immune checkpoint-related proteins.

Background: Immune checkpoint inhibition holds promise as a novel treatment for pancreatic ductal adenocarcinoma (PDAC). The clinical significance of soluble immune checkpoint (ICK) related proteins have not yet fully explored in PDAC. Methods: We comprehensively profiled 14 soluble ICK-related proteins in plasma in 70 PDAC patients and 70 matched healthy controls. Epidemiological data of all subjects were obtained through structured interviews, and patients' clinical data were retrieved from electronical health records. We evaluated the associations between the biomarkers with the risk of PDAC using unconditional multivariate logistic regression. Consensus clustering (k-means algorithm) with significant biomarkers was performed to identify immune subtypes in PDAC patients. Prediction models for overall survival (OS) in PDAC patients were developed using multivariate Cox proportional hazards regression. Harrell's concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve and calibration curve were utilized to evaluate performance of prediction models. Gene expressions of the identified ICK-related proteins in tumors from TCGA were analyzed to provide insight into underlying mechanisms. Results: Soluble BTLA, CD28, CD137, GITR and LAG-3 were significantly upregulated in PDAC patients (all q < 0.05), and elevation of each of them was correlated with PDAC increased risk (all p < 0.05). PDAC patients were classified into soluble immune-high and soluble immune-low subtypes, using these 5 biomarkers. Patients in soluble immune-high subtype had significantly poorer OS than those in soluble immune-low subtype (log-rank p = 9.7E-03). The model with clinical variables and soluble immune subtypes had excellent predictive power (C-index = 0.809) for the OS of PDAC patients. Furthermore, the immune subtypes identified with corresponding genes' expression in PDAC tumor samples in TCGA showed an opposite correlation with OS to that of immune subtypes based on blood soluble ICK-related proteins (log-rank p =0.02). The immune-high subtype tumors displayed higher cytolytic activity (CYT) score than immune-low subtype tumors (p < 2E-16). Conclusion: Five soluble ICK-related proteins were identified to be significantly associated with the risk and prognosis of PDAC. Patients who were classified as soluble immune-low subtype based on these biomarkers had better overall survival than those of the soluble immune-high subtype.

Peritoneal Dialysis Care in Mainland China: Nationwide Survey.

BACKGROUND: Peritoneal dialysis (PD) care in mainland China has been progressing in the past 10 years. OBJECTIVE: To complement information from the dialysis registry, a large-scale nationwide survey was conducted to investigate the current infrastructure and management of PD care at hospitals of different tiers. METHODS: A web-based multiple-choice questionnaire was distributed through the National Center for Nephrology Medical Quality Management and Control to PD centers of secondary and tertiary hospitals in October 2020. The 2-part survey collected the information of PD centers and the clinical management of patients on PD. A total of 788 effective surveys from 746 hospitals were voluntarily returned, and data were extracted and analyzed. RESULTS: The effective survey data covered 101,537 patients on PD, with 95% (96,460/101,537) in the tertiary hospitals. The median number of patients per PD center was 60 (IQR 21-152); this number was 32 (IQR 8-65) and 70 (IQR 27-192) for secondary and tertiary hospitals, respectively. There was a discrepancy in the availability of designated physical areas for different functions of PD care between the secondary and tertiary hospitals. The proportion of tertiary hospitals with PD training (P=.01), storage (P=.09), and procedure area (P<.001) was higher compared to secondary hospitals. PD catheter placement was performed in 96% (608/631) of the PD centers in tertiary hospitals, which was significantly higher compared to 86% (99/115) in secondary hospitals (P<.001). Automated PD was available in 55% (347/631) of the tertiary hospitals, which was significantly higher than that in secondary hospitals (37/115, 32%) according to the survey (P<.001). The most commonly performed PD module was continuous ambulatory peritoneal dialysis (772/788, 98%), followed by intermittent peritoneal dialysis (543/788, 69%). The overall reported nocturnal intermittent peritoneal dialysis was 31% (244/788); it was 28% (220/788) for continuous cycling peritoneal dialysis and 15% (118/788) for tidal peritoneal dialysis. Comparisons between the secondary and tertiary hospitals revealed no significant differences in prophylactic antibiotic use for PD catheter placement and therapeutic use for peritonitis. The first peritoneal equilibrium test was conducted in 58% (454/788) of patients at 4-6 weeks after initiation of PD, and 91% (718/788) reported at least one peritoneal equilibrium test per year. Overall, 79% (570/722) and 65% (469/722) of PD centers performed assessment for dialysis adequacy and residual kidney function, respectively; and 87% (685/788) of patients on PD were followed every 1 to 3 months for laboratory and auxiliary examinations. CONCLUSIONS: This national survey reflects the current status and disparities of PD center management in mainland China. The study results suggest that the PD care needs to be more conveniently accessible in secondary hospitals, and quality management and staff training in secondary hospitals are still in high demand.

The role of gut-dependent molecule trimethylamine N-oxide as a novel target for the treatment of chronic kidney disease.

Trimethylamine N-oxide (TMAO) is an intestinal uremic toxin molecule mainly excreted by the kidney. Therefore, the plasma TMAO concentration is significantly increased in chronic kidney disease (CKD) patients, and plasma TMAO can be cleared by dialysis. Furthermore, TMAO damage the kidney mainly through three mechanisms: oxidative stress, inflammation and endoplasmic reticulum stress. Clinical experiments have indicated that higher TMAO levels are strongly related to the elevated incidence and mortality of cardiovascular (CV) events in CKD patients. Moreover, experimental data have shown that high levels of TMAO directly aggravate atherosclerosis, thrombosis and enhance myocardial contractility, resulting in myocardial ischemia and stroke. Specially, there are currently four potential ways to reduce blood TMAO concentration or block the effect of TMAO, including reducing the intake of trimethylamine (TMA) precursors in the diet, regulating the intestinal flora to reduce TMA production, interrupting the role of flavin-dependent monooxygenase isoforms (FMOs) to reduce the generation of TMAO, and blocking the TMAO receptor protein kinase R-like endoplasmic reticulum kinase (PERK). We hope that more clinical studies and clinicians will focus on clinical treatment to reduce the concentration of TMAO and alleviate renal damage.

Evolving peritoneal dialysis care in Chinese mainland from 2010 to 2020: Comparison data from two surveys.

INTRODUCTION: Along with the peritoneal dialysis (PD)-favored policy in China and the implementation of more comprehensive PD management, PD has evolved in Chinese mainland over the last decade. Despite the existence of national registries and several provincial epidemiological descriptive studies, there was almost no national research on the changing trajectory in PD population. A comparison study, based on two national surveys that were 10 years apart, was conducted to reveal the evolvement of PD care in Chinese mainland. METHODS: Two national surveys have been done respectively in 2010 and 2020 to capture the epidemiological status, application of different modalities, management of perioperative infection, and long-term complications among PD patients. RESULTS: In the study with 730 participating hospitals (n = 14,912 PD patients) in 2010 and 746 hospitals (n = 101,537) in 2020, prevalent PD patients have increased in the past 10 years with increased numbers of PD patients in both secondary (average 5 ± 16 vs. 43 ± 41, p < 0.01) and tertiary hospitals (32 ± 53 vs. 153 ± 215, p < 0.01). Automated PD has been accessible in 0.4% of all hospitals, only in tertiary centers in 2010 and its application increased to 51% in 2020. PD centers have become more engaged in PD catheter placement, treated properly for the PD-related infection, and carried out the follow-up in compliance with the national protocols. CONCLUSIONS: Our study indicates that over the past decade, the prevalent PD population has quickly expanded with increased APD availability in Chinese mainland. The management of PD patients has become better conforming to the guidelines and long-term follow-up of patients have remained stable. Further studies are warranted to evaluate whether the rapidly changing paradigm of PD could translate into the socio-economic benefits in the society.

Enhancement of the light output efficiency and thermal stability of AlGaN-based deep-ultraviolet light-emitting diodes with Ag-nanodot-based p-contacts and an 8-nm p-GaN cap layer.

The efficiency of AlGaN-based deep-ultraviolet light-emitting diodes (DUV LEDs) is limited by the high absorption issue of the p-GaN contact layer or poor contact properties of the transparent p-AlGaN contact layer. Enhancement of the light output efficiency and thermal stability of DUV LEDs with an emission wavelength of 272 nm was investigated in this work. Ag nanodots on an 8-nm p-GaN cap layer were used to form ohmic contact, and Al and Mg reflective mirrors were employed to enhance the light output power (LOP) of DUV LEDs. However, serious deterioration of LOP occurred after the high-temperature process for the LEDs with Al and Mg reflective mirrors, which can be attributed to the damage to the ohmic contact properties. A Ti barrier layer was inserted between the Ag/p-GaN and Al layers to prevent the degeneration of ohmic contact. The wall-plug efficiency (WPE) of DUV LEDs fabricated by the Ag-nanodot/Ti/Al electrode is 1.38 times that of LEDs fabricated by adopting a thick Ag layer/Ti/Al at 10 mA after a high-temperature process. The Ag-nanodot/Ti/Al electrode on thin p-GaN is a reliable technology to improve the WPE of DUV LEDs. The experimental and simulated results show that the ohmic contact is important for the hole-injection efficiency of the DUV LEDs when p-GaN is thin, and a slight increase in the contact barrier height will decrease the WPE drastically. The results highlighted the importance of thermally stable ohmic contacts to achieve high-efficiency DUV LEDs and demonstrated a feasible route for improving the LOP of DUV LEDs with a thin p-GaN cap layer and stable reflective electrodes.

Social inequalities in COVID-19 mortality by area and individual-level characteristics in Canada, January to July/August 2020: Results from two national data integrations.

Background: Despite early reports of social determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) burden, national Canadian reporting on COVID-19 inequalities has been limited. The objective of this study is to describe inequalities in COVID-19 mortality in Canada using preliminary data, as part of the Pan-Canadian Health Inequalities Reporting Initiative. Methods: Two provisional Canadian Vital Statistics Death Database integrations were used. Data concerning deaths between January 1 and July 4, 2020, among private-dwelling residents were linked to individual-level data from the 2016 short-form Census, and disaggregated by sex and low-income status, dwelling type, household type and size. Data concerning deaths between January 1 and August 31, 2020 linked to 2016 Census area data were disaggregated by sex and neighbourhood ethno-cultural composition quintiles (based on the proportion of residents who are recent immigrants, visible minorities, born outside of Canada, with no knowledge of English or French), income quintiles and urban residence. The COVID-19 age-standardized mortality rate (per 100,000 population) differences and ratios between groups were estimated. Results: As of July/August 2020, apartment dwellers, residents of urban centres, neighbourhoods with the highest ethno-cultural composition or lowest income experienced 14 to 30 more COVID-19-related deaths/100,000 compared with reference groups (residents of single-detached homes, outside of urban centres, with lowest ethno-cultural concentration or highest income, respectively). Per 100,000 population, sex/gender inequalities were also larger in these four groups (11 to 18 more male than female deaths) than in the reference groups (two to four more male than female deaths). Conclusion: These findings highlight how populations facing socioeconomic disadvantage have experienced a higher overall burden of deaths. Areas for future research are discussed to guide health equity-informed pandemic response.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Optimization of annealing conditions for Ag/p-GaN ohmic contacts.

The electrical and optical properties of Ag/p-GaN contacts have been investigated as a function of the annealing temperature, oxygen concentration, and annealing time. Specific contact resistance (ρ c) values as low as 1.2 × 10-4 Ω·cm2 were obtained from the Ag/p-GaN contact annealed at 400 °C for 60 s in ambient O2/N2 (1:10). We found that the participation of oxygen improves the formation of ohmic contacts. Oxygen might remove the H in Mg-H complexes to activate the Mg acceptors and enhance Ga out-diffusion to form an Ag-Ga solid solution. We also found that the reflectivity of the Ag layer decreases with increasing annealing temperature in the O2-containing ambient environment. Thus, an optimal annealing condition of Ag/p-GaN for blue and green LEDs is suggested based on these results. We also used the suggested annealing conditions to form ohmic contacts on DUV LEDs and achieved good electrical performance. The forward voltages of UVC LEDs fabricated with annealed Ag contacts were 6.60 V (7.66 V) at a 40 mA (100 mA) injection current.

Multi-Task Learning-Based Immunofluorescence Classification of Kidney Disease.

Chronic kidney disease is one of the most important causes of mortality worldwide, but a shortage of nephrology pathologists has led to delays or errors in its diagnosis and treatment. Immunofluorescence (IF) images of patients with IgA nephropathy (IgAN), membranous nephropathy (MN), diabetic nephropathy (DN), and lupus nephritis (LN) were obtained from the General Hospital of Chinese PLA. The data were divided into training and test data. To simulate the inaccurate focus of the fluorescence microscope, the Gaussian method was employed to blur the IF images. We proposed a novel multi-task learning (MTL) method for image quality assessment, de-blurring, and disease classification tasks. A total of 1608 patients' IF images were included-1289 in the training set and 319 in the test set. For non-blurred IF images, the classification accuracy of the test set was 0.97, with an AUC of 1.000. For blurred IF images, the proposed MTL method had a higher accuracy (0.94 vs. 0.93, p < 0.01) and higher AUC (0.993 vs. 0.986) than the common MTL method. The novel MTL method not only diagnosed four types of kidney diseases through blurred IF images but also showed good performance in two auxiliary tasks: image quality assessment and de-blurring.

Local hepcidin increased intracellular iron overload via the degradation of ferroportin in the kidney.

BACKGROUND: Hepcidin is a key regulator of iron homeostasis. Some studies showed that exogenous hepcidin decreased the expression of divalent metal transporter (DMT1) rather than ferroportin(FPN1) to regulate renal iron metabolism. This study explored the effects of hepcidin synthesized by the kidney and its mechanism of iron regulation. METHODS: In the in vivo experiments, mice were divided into a unilateral ureter obstruction (UUO) model group and a sham operation group, and mice in the UUO model group were sacrificed on days 1, 3, 5 and 7. The expression of renal hepcidin, FPN1, DMT1 and the retention of renal iron were studied. In the in vitro experiments, we overexpressed hepcidin in HK-2 cells. Then we tested the expression of renal hepcidin, FPN1, DMT1 and observed the production of intracellular ferrous ions. RESULTS: Renal hepcidin expression was consistently higher in the UUO group than in the sham group from the first day. The expression of FPN1 gradually decreased, and the expression of DMT1 gradually increased in the UUO model. Intracellular ferrous ions significantly increased on the first day of the UUO model. In hepcidin overexpressed HK-2 cells, the expression of FPN1 was decreased, while the expression of DMT1 has no significant change. In addition, production of intracellular ferrous ions increased. CONCLUSION: local hepcidin can regulate iron metabolism in the kidney by adjusting the expression of FPN1.

Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats.

Stem cell therapies for intervertebral disc degeneration have been demonstrated as a promising strategy. Previous studies have shown that human nucleus pulposus cell- (NPC-) derived exosomes can induce the differentiation of mesenchymal stem cells (MSCs) into NP-like cells in vitro. However, the mechanism of MSC differentiation into NP-like cells with the induction of NPC exosomes is still unclear. Here, we verified the induction effects of NPC exosomes on the differentiation of MSCs into NP-like cells. In addition, the Notch1 pathway was downregulated in this process. Then, DAPT and soluble Jagged1 (SJAG) were applied to inhibit or enhance the expression of the Notch1 pathway, respectively, resulting in the upregulation or downregulation of collagen II, aggrecan, and Sox9 in MSCs. Knocking down of Notch1 protein facilitated the effects of NPC exosomes on the differentiation of MSCs into NP-like cells. NPC exosomes were more effective than an indirect coculture system in terms of the differentiation of MSCs into NP-like cells. Inhibition of NPC exosome secretion with Rab27a siRNA prevented the induction effects of an indirect coculture system on the differentiation of MSCs into NP-like cells. Transwell migration assays revealed that NPC exosomes could promote the migration of MSCs. Taken together, the Notch1 pathway was negatively associated with the differentiation of MSCs into NP-like cells with the treatments of NPC exosomes. Inhibition of the Notch1 pathway facilitates NPC exosome-induced differentiation of MSCs into NP-like cells in vitro. NPC exosomes play a key role in the differentiation of MSCs into NP-like cells in an indirect coculture system of NPCs and MSCs.

A Case-Control Study of Risk Factors for Salivary Gland Cancer in Canada.

Aim. To assess the effect of various lifestyle risk factors on the risk of salivary gland cancer in Canada using data from a population-based case-control study. Methods. Data from a population-based case-control study of 132 incident cases of salivary gland cancer and 3076 population controls were collected through self-administered questionnaire and analysed using unconditional logistic regression. Results. Four or more servings/week of processed meat product was associated with an adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) of 1.62 (1.02-2.58). Nonsignificantly increased ORs were also related to obesity, >7 drinks/week of alcohol consumption, and occupational exposure to radiation. Furthermore, nonsignificantly decreased ORs were found to be associated with high education level (>12 years) (OR = 0.65), high consumption of spinach/squash (OR = 0.62) and all vegetables/vegetable juices (OR = 0.75), and >30 sessions/month of recreational physical activity (OR = 0.78). Conclusions. This study suggests positive associations with consumption of processed meat, smoking, obesity, alcohol drinking, and occupational exposure to radiation as well as negative associations with higher education, consumption of spinach/squash, and physical activity, which suggest a role of lifestyle factors in the etiology of salivary gland cancer. However, these findings were based on small number of cases and were nonsignificant. Further larger studies are warranted to confirm our findings.

Delayed iatrogenic diaphragmatic hernia after thoracoscopic lobectomy.

Postoperative iatrogenic diaphragmatic hernia after thoracoscopic lobectomy is extremely rare. We present a 55-year-old female patient who developed an iatrogenic diaphragmatic hernia with gastric perforation several months after VATS (video-assisted thoracic surgery) left upper lobectomy with systematic lymphadenectomy. During the readmission, urgent laparotomy was performed. Intraoperatively, the choledochoscopy was introduced into left thoracic cavity through the diaphragmatic defect for dissecting the secondary inflammatory adhesions and achieving satisfactory hemostasis. It appears to be an efficient and feasible approach for the patients who have been diagnosed as delayed diaphragmatic hernia concomitant with remarkable intra-abdominal findings and have a history of thoracic surgery. We consider that delayed-onset diaphragmatic hernia should be suspected in patients complaining of nausea or vomiting after VATS procedure, although it is very rare.

Postoperative Regulatory T-Cells and Natural Killer Cells in Stage I Nonsmall Cell Lung Cancer Underwent Video-assisted Thoracoscopic Lobectomy or Thoracotomy.

BACKGROUND: Regulatory T-cells (Treg) play key roles in suppressing cell-mediated immunity in cancer patients. Little is known about perioperative Treg fluctuations in nonsmall cell lung cancer (NSCLC). Video-assisted thoracoscopic (VATS) lobectomy, as a minimal invasive procedure for treating NSCLC, may have relatively less impact on the patient's immune system. This study aimed to observe perioperative dynamics of circulating Treg and natural killer (NK) cell levels in NSCLC patients who underwent major lobectomy by VATS or thoracotomy. METHODS: Totally, 98 consecutive patients with stage I NSCLC were recruited and assigned into VATS or thoracotomy groups. Peripheral blood samples were taken on 1-day prior to operation, postoperative days (PODs) 1, 3, 7, 30, and 90. Circulating Treg and NK cell counts were assayed by flow cytometry, defined as CD4 + CD25 + CD127 low cells in CD4 + lymphocytes and CD56 + 16 + CD3- cells within CD45 + leukocytes respectively. With SPSS software version 21.0 (SPSS Inc., USA), differences between VATS and thoracotomy groups were determined by one-way analysis of variance (ANOVA), and differences between preoperative baseline and PODs in each group were evaluated by one-way ANOVA Dunnett t-test. RESULTS: In both groups, postoperative Treg percentages were lower than preoperative status. No statistical difference was found between VATS and thoracotomy groups on PODs 1, 3, 7, and 30. On POD 90, Treg percentage in VATS group was significantly lower than in thoracotomy group (5.26 ± 2.75 vs. 6.99 ± 3.60, P = 0.012). However, a higher level of NK was found on all PODs except on POD 90 in VATS group, comparing to thoracotomy group. CONCLUSIONS: Lower Treg level on POD 90 and higher NK levels on PODs 1, 3, 7, 30 in VATS group might imply better preserved cell-mediated immune function in NSCLC patients, than those in thoracotomy group.