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The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
Subject(s)
Humans , Mice , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Acrylamides/pharmacology , ErbB Receptors/metabolism , Cell Line, Tumor , CD47 Antigen/therapeutic useABSTRACT
The standardized residency training is an important stage in the training of physicians. Shanghai East Hospital has explored the system of the whole-process tutor management in the residency training. To explore the specific methods of carrying out the whole-process tutor training for residents in the whole hospital, gradually the whole-process tutor system is built with qualification certification, mutual selection of teachers and students, tutor empowerment, plan implementation and assessment and evaluation. Meanwhile, a supporting informatization platform is being developed to provide necessary tool support for the implementation and promotion of the whole-process tutor of residency training. And information tools are used to carry out implementation management, process optimization and quality monitoring, so as to form a closed management loop.
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Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.
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OBJECTIVE@#To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening.@*METHODS@#A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development.@*RESULTS@#Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development.@*CONCLUSION@#SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.
Subject(s)
Humans , Infant, Newborn , Amino Acid Metabolism, Inborn Errors/genetics , Carnitine , Neonatal Screening/methodsABSTRACT
The instep flap and medialis pedis flap are both originate based on the medial plantar artery. The medialis pedis flap is based from the deep branch and the instep flap is based from the superficial branch. To increase the axial rotation, it is acceptable to ligate the lateral plantar artery. However, this can partially affect the blood supply of the plantar metatarsal arch. We restored the blood flow with a vein graft between the posterior tibial artery and the ligated stump. From 2012 to 2020, 12 cases of heel reconstruction, including seven instep flaps and five medialis pedis flaps, were performed with ligation of the lateral plantar artery. The stump of the lateral plantar artery was restored with a vein graft and between the posterior tibial artery and the ligated stump. Patients were followed for 18 months. Long-term results showed the vascular restoration of the lateral plantar artery remained patent demonstrated by doppler ultrasonography. Restoring blood flow to the lateral plantar artery maintains good blood supply to the toes. If the patient in the future develops a chronic degenerative disease, with microvascular complications, bypass surgery can still be performed because of the patency of both branches.
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Objective@#To evaluate the quality of tandem mass spectrometry (MSMS) screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021.@*Methods@#The data pertaining to MSMS screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The percentage of MSMS screening, percentage of recall of suspected screening-positive infants and incidence of neonatal inherited metabolic diseases were analyzed retrospectively to evaluate the quality of MSMS screening for inherited metabolic diseases.@*Results@#A total of 4 706 916 newborns were screened among 8 297 039 live births by MSMS in Zhejiang Province from 2009 to 2021, and the percentage of MSMS screening increased from 5.48% to 97.54%, with a mean percentage of 56.73%. Of 46 838 suspected screening-positive infants, 45 527 infants were recalled, and the percentage of recall increased from 94.57% to 98.62%, with a mean percentage of 97.20%. A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535, and the incidence rates of amino acid metabolic disorder, fatty acid oxidation metabolic disorder and organic acid metabolic disorder were 1/11 767, 1/13 763 and 1\15 902, respectively. Of the 11 cities in Zhejiang Province, the highest percentage of tandem mass spectrometry screening for inherited metabolic diseases was found in Hangzhou City (83.01%), and the highest percentage of recall of suspected screening-positive infants was se en in Zhoushan City (99.08%). @*Conclusions@#A high percentage of MSMS screening for neonatal inherited metabolic diseases was observed in Zhejiang Province from 2009 to 2021; however, there was a region-specific percentage of screening, and the recall of suspected screening-positive infants remains to be improved.
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Objective@#To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabolic diseases during neonatal screening in Zhejiang Province from 2009 to 2021, so as to provide insights into the management of birth defects.@*Methods@#The medical records of infants with definitive diagnosis of inherited metabolic diseases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The prevalence, genotypes and prognosis of inherited metabolic diseases were analyzed. @*Results@#A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535. There were 400 infants with amino acid metabolic disorders (AAD), 342 infants with fatty acid oxidation metabolic disorders and 296 infants with organic acid metabolic disorders (OAD), with incidence of 1/11 767, 1/13 763 and 1\15 902, respectively. There were 32 types of diseases, including 13 types of AAD, 8 types of FAOD and 11 types of OAD identified, and phenylketonuria and tetrahydrobiopterin deficiency (PKU/BH4D), primary carnitine deficiency (PCD) and methylmalonic academia (MMA) were detected as the most common forms of AAD, FAOD and OAD, with incidence of 1/20 827, 1/24 262 and 1\49 030, respectively. A total of 789 infants received genetic testing (76.01%), and genetic testing was performed among 70.00% of infants with AAD, 83.04% of infants with FAOD and 76.01% of infants with OAD. The c.728G >A (p.R243Q) variant was the most common mutation in infants with PKU (29.17%), c.1400C>G (p.S467C) variant was the most common mutation in infants with PCD (33.46%), c.609G>A (p.W203X) variant was the most common mutation in infants with combined MMA (40.00%), and c.1663G>A (p.A555T) variant was the most common mutation in infants with MMA (17.86%). Among the 997 infants (96.05%) with successful follow-up, 973 infants (93.74%) had normal intelligence and physical developments, and 41 infants died (3.95%), including 9 deaths due to AAD, 15 deaths due to FAOD and 17 deaths due to OAD. @*Conclusions @#The incidence of PKU, PCD and MMA was high among infants with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with c.728G>A (p.R243Q), c.1400C>G (p.S467C) and c.609G>A (p.W203X) variants as common gene mutations, respectively. Most infants with inherited metabolic diseases had a favorable prognosis; however, the mortality of OAD was relatively high.
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The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.
Subject(s)
Tea/chemistry , Beverages/microbiology , Camellia sinensis , Fermentation , Acids , Amino Acids , GlucoseABSTRACT
Background@#Impacts of exposure are generally monitored and recorded after injuries or illness occur. Yet, absence of conventional after-the-effect impacts (i.e., lagging indicators), tend to focus on physical health and injuries, and fail to inform if workers are not exposed to safety and health hazards. In contrast to lagging indicators, leading indicators are proactive, preventive, and predictive indexes that offer insights how effective safety and health. The present study is to validate an extended Voluntary Protection Programs (VPP) that consists of six leading indicators. @*Methods@#Questionnaires were distributed to 13 organizations (response rate = 93.1%, 1,439 responses) in Taiwan. Cronbach α, multiple linear regression and canonical correlation were used to test the reliability of the extended Voluntary Protection Programs (VPP) which consists of six leading indicators (safe climate, transformational leadership, organizational justice, organizational support, hazard prevention and control, and training). Criteria-related validation strategy was applied to examine relationships of six leading indicators with six criteria (perceived health, burnout, depression, job satisfaction, job performance, and life satisfaction). @*Results@#The results showed that the Cronbach's α of six leading indicators ranged from 0.87 to 0.92. The canonical correlation analysis indicated a positive correlation between the six leading indicators and criteria (1st canonical function: correlation = 0.647, square correlation = 0.419, p < 0.001). @*Conclusions@#The present study validates the extended VPP framework that focuses on promoting safety and physical and mental health. Results further provides applications of the extended VPP framework to promote workers' safety and health.
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OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.
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Biliary complications, especially the ischemic-type biliary lesions (ITBL), are the main causes of mortality and retransplantation for patients undergoing liver transplantation. In recent years, the application of marginal donor livers such as livers from donor of cardiac death and fatty liver leads to high incidence of ITBL. As a result, the treatment and prevention of ITBL after liver transplantation become a research hotspot. Based on the global research progress and the clinical experience of their liver transplantation center, the authors investigate the treatment and prevention of ITBL after liver transplantation in the donation after cardiac death era.
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BACKGROUND@#Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation.@*RESULTS@#The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD.@*CONCLUSIONS@#From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.
Subject(s)
Adult , Humans , Cross-Sectional Studies , Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease/epidemiology , Nutrition Surveys , PrevalenceABSTRACT
Objective:To enable the low-seniority medical personnel having the ability of disposing of difficult airway properly by mastering the knowledge of basic airway management through Airway Management Simulation Training and using all kinds of airway treatment tools.Methods:The senior medical simulation training tutors were selected, and the Airway Management Simulation Training Project Team was formed to develop the training course. Through combination of video teaching and practice of simulated teaching forms, we taught 219 trainees the airway management training course. And the feasibility and effectiveness of the course were evaluated by KE's evaluation method.Results:The course of "oriental airway simulation training" was successfully developed, and the complete course package was delivered, including bilingual airway management trainee textbook, Airway Management Simulation Training tutor manual, standardized teaching video and so on. After this simulation training, students had a good grasp of airway management skills, and more than 90.86% of the students' skills assessment resulted in more than 80 points. The overall satisfaction of the students was more than 97%, and 99% participants said that the training helped them enhance their confidence in clinical treatment, and 98% participants said that the training should be promoted among medical staff.Conclusion:The course of "oriental airway simulation training" which is made up of the combination of airway technical training, correct clinical decision-making and reality simulation, has significantly improved the airway management skills, enhanced the self-confidence of low-seniority medical staffs and improved patients' safety.
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In this report, we discuss the postoperative protocol for patients undergoing lymphaticovenous anastomosis (LVA) in our unit. Immediately after LVA, the incision site is closed over a small Penrose drain and a simple gauze dressing is applied without compression. In the first 5 days, ambulation is allowed, but limb elevation is actively encouraged to promote lymphatic flow across the newly formed anastomosis. Prophylactic antibiotics are routinely given to prevent infection because this patient group is susceptible to infections, which could trigger thrombosis in the anastomosis.
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In this report, we discuss the postoperative protocol for patients undergoing lymphaticovenous anastomosis (LVA) in our unit. Immediately after LVA, the incision site is closed over a small Penrose drain and a simple gauze dressing is applied without compression. In the first 5 days, ambulation is allowed, but limb elevation is actively encouraged to promote lymphatic flow across the newly formed anastomosis. Prophylactic antibiotics are routinely given to prevent infection because this patient group is susceptible to infections, which could trigger thrombosis in the anastomosis.
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OBJECTIVE@#To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS).@*METHODS@#The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression.@*RESULTS@#Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05).@*CONCLUSION@#frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.
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Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.
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Objective To analyze the stage characteristics in the exercise behavior improvement of college students and explore the role of Process in the exercise behavior change based on the transtheoretical model, providing basis for the stage-matched intervention for the exercise behavior of college students. Methods There were 932 students who completed the questionnaires, from 5 universities in Shanxi Province were selected by using a stratified random cluster sampling method. Descriptive analysis was used to describe the exercise behavior of college students. Variance analysis and multivariate Logistic regression model were used to analyze the difference of the process of with stage of change among college students’ physical exercise. Multivariate variance analysis was used to analyze how personal characteristics affect process of change. Results Among all participants, 89.4% students knew the importance of physical exercise, and 29.4% students were satisfied with their physical exercise condition. The distribution of students’ physical exercise stage showed an inverted U-shape with left-side peak, and there was a significant difference between gender( 2=54.657, P<0.001). There were significant stage characteristics in the process of students' exercise behavior, gender had a significant main effects on mutual aid relation(F=7.400, P=0.07)and conscious control (F=7.778, P=0.005), gender and grade had interaction effects on social release (F=3.614, P=0.013). Conclusions The college students' exercise behavior showed the characteristics of “knowing but not to do”, which conformed to the Transtheoretical model. It is essential to develop targeted phased exercise intervention strategies according to the relationship between change of phase and change of procedure.
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Objective To clarify the depression status of empty-nest elderly in Shanxi Province, to explore the related influencing factors by structural equation model, and to provide scientific basis for the prevention and intervention of depression for empty nesters. Methods A questionnaire survey was conducted among 4 901 empty-nest elderly in Shanxi Province by self-rating depression scale and general situation questionnaire, and the model was established. Results The prevalence of depressive symptoms among empty nesters in Shanxi Province was 64.21%. The model demonstrated that health status had a direct impact on depressive symptoms (P=0.028), the total effect was -0.978; the effect of economic status on depressive symptoms was 0.086 (P=0.030), and social function had no significant impact on depressive symptoms (P=0.173), which could affect depressive symptoms through affecting health status and economic status. There was a significant correlation between the three latent variables (P<0.05). Health status had the strongest correlation with social function (r=0.942), followed by economic status (r=0.718), and the correlation between social function and economic status was 0.683. Conclusions In this research, most of the empty-nest elderly suffer from depressive symptoms. Health status is the most direct and important influencing factor of depressive symptoms in empty nesters. Social function affects depressive symptoms through influencing health status and economic status.
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Hypospadias is a congenital malformation of the male genitalia. The reconstructive objectives are to obtain voiding with laminar flow and satisfactory sexual function. Several urethroplasty techniques have been described, but for perineal or revisional cases no single technique has shown robust success. In this study, we describe the expanded use of intestinal flaps for urethral reconstruction and report a peculiar request from a patient to undergo peno-urethral separation after successful hypospadias repair with a free ileum flap. A 51-year-old male patient with perineal hypospadias underwent several urethral reconstructive procedures with poor outcomes. A free ileum flap was attempted as a substitute for the urethra. Following successful reconstruction, separation of the neo-urethra (ileum) from the penile body was performed to address the patient's sexual expectations. A free ileum flap proved to be a reliable urethral substitute in perineal hypospadias reconstruction, with a successful outcome. The peno-urethral separation with the creation of an “accessory penis,” however peculiar, optimized the results in terms of both sexual and urinary function. Anatomical restoration of the urethra and patient-reported expectations are the key to successful hypospadias reconstructive procedures. Sexual function outcomes and the patient's perception of success should not be underestimated, even when urinary function has been restored.