Use of Intracameral Tissue Plasminogen Activator During Uveitic Cataract Surgery.

PURPOSE: To report the outcomes of intracameral tissue plasminogen activator (tPA) use during uveitic cataract surgery. DESIGN: Retrospective case series from a single United States tertiary center of 36 eyes from 31 consecutive patients with established uveitis who received intraoperative intracameral tPA during cataract surgery between 2016 and 2020. RESULTS: Mean visual acuity (VA) improved from logMAR 1.0 ± 0.7 preoperatively to logMAR 0.7 ± 0.8 by POM12. VA improved from baseline postoperatively (POM1 p = 0.0002, POM6 p = 0.006 and POM12 p = 0.007). Minimal to no anterior chamber inflammation was achieved in 47.2% of the eyes by POW1 and 80.0% of the eyes by POM1. Mean clock-hours of posterior synechiae improved from 8.2 ± 3.8 preoperatively to 0.1 ± 0.6 by POM12. Six eyes developed hyphema and/or vitreous hemorrhage, four of which resolved spontaneously. CONCLUSIONS: Adjunctive intracameral tPA during uveitic cataract surgery improves VA and intraocular inflammation, but risks postoperative hemorrhage. Intraoperative tPA as adjunctive anti-inflammatory therapy warrants randomized prospective studies.

Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice.

Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gram-negative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/PFKFB3/NF-κB inflammatory pathway.

[Research progress of follow-up monitoring design in mega cohort].

With the increasing demand to study the cause of complex diseases, mega cohort has gradually replaced the traditional small sample cohort and become the hotspot of epidemiological research. Follow-up is the essential step in a cohort study to obtain the information about the onset and death of diseases, migration or loss of follow-up of the cases. Its quality has a direct impact on the conclusions of cohort study. Therefore, it is necessary to develop a reasonable follow-up monitoring program for a mega cohort.In this paper, we summarized the contents and methods of the follow-up monitoring program in the mega cohorts at home and abroad, which aimed to provide suggestions for the new cohort and improve the follow-up program for the existing cohort.

Alleviating effect of mulberry leaf 1-deoxynojirimycin on resistin-induced hepatic steatosis and insulin resistance in mice.

Resistin is upregulated in obese humans and mice, and elevated serum resistin induces insulin resistance and hepatic steatosis. Previous studies have revealed that mulberry 1-deoxynojirimycin (DNJ) is important for a variety of physiological processes, especially carbohydrate and lipid metabolism. However, it remains unclear whether DNJ has a positive effect on insulin resistance and hepatic steatosis, and what the exact mechanism is. Male C57BL/6J mice were treated with resistin with or without DNJ. DNJ reversed the homeostasis model assessment of insulin resistance (HOMA-IR)-induced by resistin and significantly decreased triglyceride levels both in the serum and liver. A histological analysis demonstrated that lipid accumulation significantly decreased in the DNJ group compared to the resistin group. A mechanistic analysis showed that DNJ significantly inhibited the resistin-induced decline in enzyme activities of hormone-sensitive lipase (HSL) and hepatic lipase (HL) in serum and lipoprotein lipase (LPL) in liver. FAS and Acox13α were significantly altered by resistin but restored by DNJ. Furthermore, DNJ partially but significantly restored insulin-stimulated glucose uptake compared with the resistin group, suggesting that DNJ reversed the insulin sensitivity impaired by hyperresistinemia. Treatment of AML12 cells with DNJ significantly restored the expression level and phosphorylation of Akt. The transcriptional levels of InsR and IRS1, as well as the protein levels of InsR and Glut4 and phosphorylation of PI3K and GSK3ß, were also normalized in the DNJ-treated group. In conclusion: mulberry DNJ significantly alleviated liver steatosis and insulin resistance in hyperresistinemia.

First-line Cemiplimab versus Standard Chemotherapy in Advanced Non-small Cell Lung Cancer Patients with at Least 50% Programmed Cell Death Receptor Ligand-1 Positivity: Analysis of Cost-effectiveness.

AIMS: The EMPOWER-Lung 1 trial showed that cemiplimab significantly prolongs the duration of progression-free survival and overall survival in advanced non-small cell lung cancer (NSCLC) patients with at least 50% programmed cell death receptor ligand-1 (PD-L1) positivity, yet the financial burden may limit its use. The aim of the present study was to evaluate the cost-effectiveness of cemiplimab versus chemotherapy in a US setting. MATERIALS AND METHODS: A Markov model, with three mutually exclusive health states, was used to compare the expected health outcomes and cost of cemiplimab with chemotherapy. Survival data and transition probabilities were collected from the EMPOWER-Lung 1 trial. Utility values and costs are publicly available from open sources. One-way and probabilistic sensitivity analyses were conducted in both the whole population and subgroups to test the robustness of the parameters and structure. RESULTS: Treatment of NSCLC with cemiplimab yielded an extra 1.07 quality-adjusted life years (QALYs) at an additional cost of $98 211 compared with chemotherapy, associated with an incremental cost-effectiveness ratio of $91 891/QALY and an incremental net health benefit of 0.087 QALYs at a willingness to pay threshold of $100 000/QALY. The probabilistic sensitivity analysis indicated that cemiplimab provided an 83.2% probability of being cost-effective. One-way sensitivity analysis suggested that the price of cemiplimab was the chief driver in this model. A subgroup analysis showed that cemiplimab was the preferred incremental net health benefit in more than half of the subgroups, including patients with squamous type disease and metastases. CONCLUSIONS: Cemiplimab is a cost-effective option in the first-line treatment of NSCLC in patients who are at least 50% PD-L1 positive from an American perspective.

Adlay, an ancient functional plant with nutritional quality, improves human health.

Adlay (Coix lacryma-jobi L.), a crop closed related to maize (Zea mays L.) and sorghum (Sorghum bicolor L.), originated in tropical/subtropical regions of Asia and Africa; southwest China primary center of this plant's origin, evolution and migration. Adlay is a traditional high-value minor crop used for both medicinal and dietary purposes. Adlay has anti-tumor, anti-bacterial, anti-inflammatory, analgesic, blood sugar-lowering, and blood lipid-lowering effects. To clarify the main bioactive components and phytochemical compounds and to fully explore their utility, this review summarizes the research done on the main functional ingredients of adlay, including amino acids and proteins, oils, vitamins and minerals, polysaccharides, and polyphenols. This study also highlighted the application of genome sequencing to tailor nutrient-rich adlay cultivars and nutraceutical product development. Additionally, the acquisition of high-density genomic data combined with next-generation phenotypic analysis will undoubtedly improve our understanding of the potential genetic regulation of adlay nutraceutical traits. This review provides new insights and ideas for the research of adlay in comparison and evolutionary genomics, and a useful reference for molecular breeding and genetic improvement of this important minor crop.

[Comparison between transoral radiofrequency coblation surgery and open partial laryngectomy for the treatment of supraglottic laryngeal carcinoma].

Objective: To explore the feasibility and efficacy of radiofrequency coblation assisted transoral surgery for the treatment of supraglottic laryngeal carcinoma by comparing with concurrent patients treated with conventional transcervical approach. To clarify the advantages of different surgical methods and to summarize the experience of supraglottic carcinoma radiofrequency ablation. Methods: Forty-six patients with supraglottic laryngeal carcinoma treated in department of otorhinolaryngology head and neck surgery, Peking University First Hospital from March 2014 to January 2021 were analyzed retrospectively. Among them(43 males, 3 females, aged from 45 to 79 years old), 23 patients were treated with radiofrequency coblation and 23 patients with partial laryngectomy with conventional transcervical approach. The operation time, intra-operative blood loss volume, recovery time, inpatient total medical cost and follow-up information of the two groups were analyzed. SPSS 26.0 software was used for statistical analysis. Results: There were no significant differences in age, gender, TNM staging,tumor staging and postoperative radiotherapy between the two groups (all P>0.05).The operation time, intra-operative blood loss volume, recovery time, inpatient total medical cost of the RFC-TOS group were110.0(60.0,150.0)min,5.0(5.0,30.0)ml,3.0(2.0,5.0)days,6.0(4.0,14.0)days and 26 100.7(16 145.5,47 044.4)yuan. The data of conventional transcervical approach group were 205.0(156.5,272.3)min, 150.0(50,200) ml, 18.0(16.3,22.8)days and 56520.1(440 992.5,67 109.9)yuan, (Z=-4.03, -4.94, -4.97, -4.98 and -4.13;all P<0.001).The 5-year local control rate, disease-specific survival rate and overall survival rate of the two groups were 86.96%,95.65%,91.30% and 86.96%,91.30%,73.90% renspectively, which had no significant difference between the two groups(all P>0.05). Conclusions: Compared with conventional transcervical surgeries, RFC-TOS could be a reliable new surgical option for organ-function preservation strategy in the treatment of supraglottic laryngeal carcinoma.The RFC is a suitable new technique and deserving more multi-center clinical trials for its clinical promotion.

Application of random sample consensus method for parameter estimation of reflectometry density profile in toroidal plasma.

Microwave reflectometry diagnostics have been widely used to measure density profiles in fusion plasma. However, the high sensitivity of the diagnostics to plasma turbulence often results in large radial deviations in the edge density profile and causes difficulty in profile evaluation. To improve the performance of profile evaluation, a modified RANdom SAmple Consensus (RANSAC) method has been applied to fit the density profiles measured by reflectometry on the experimental advanced superconducting tokamak. Compared with the traditional least-squares method, the modified RANSAC method is much more efficient and robust in fitting the experimental profiles. Furthermore, a combination of RANSAC and a genetic algorithm (GA-RANSAC) is used to further optimize the profile evaluation procedure. The results show that this GA-RANSAC method yields better performance and stabler convergence than the modified RANSAC alone.

Construction of an MnO2 nanosheet array 3D integrated electrode for sensitive enzyme-free glucose sensing.

MnO2 based electrochemical enzyme-free glucose sensors remain significantly limited by their low electronic conductivity and associated complex preparation. In this paper, an MnO2 nanosheet array supported on nickel foam (MnO2 NS/NF) was prepared using a simple hydrothermal synthesis and employed as a 3D integrated electrode for enzyme-free glucose detection. It was found that MnO2 NS/NF shows high performance with a wide linear range from 1 µM to 1.13 mM, a high sensitivity of 6.45 mA mM-1 cm-2, and a low detection limit of 0.5 µM (S/N = 3). Besides, MnO2 NS/NF shows high selectivity against common interferences and good reliability for glucose detection in human serum. This work demonstrates the promising role of MnO2 NS/NF as an efficient integrated electrode in enzyme-free glucose detection with high performance.

[Overview of the role of inhaled corticosteroids in chronic obstructive pulmonary disease from evolution of guidelines].

In the treatment of stable chronic obstructive pulmonary disease (COPD), international guidelines have updated the recommendations for inhaled corticosteroids (ICS) based on the accumulated clinical evidences, and the understanding has gone further from "controversy" to "affirmation" until the presence of the lastest guideline that indicates patients are divided into two phenotypes according to the clinical characteristics of dyspnea and acute exacerbation for adjustments in treatment strategy, and for patients with frequent acute exacerbations during the last one year, combined with their blood eosinophil counts, the individualized treatments including ICS are recommended.

EGF receptor inhibitors comprehensively suppress hepatitis B virus by downregulation of STAT3 phosphorylation.

Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 µM. It also reduced the syntheses of viral antigens at concentrations of 2.5 µM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.

[Effect of cognitive impairment on social function and quality of life in chronic schizophrenia].

Objective: To clarify the effect of cognitive impairment on social function and quality of life of chronic schizophrenia, and provide clinical cognitive strategies for improving the social function and quality of life of patients with schizophrenia. Methods: Atotal of 158 patients with chronic schizophrenia were selected from May 2017 to October 2017 in the Psychiatry Department of the Third Affiliated Hospital of Sun Yat-sen University received psychological assessments, such as, MATRICS Consensus Cognitive Battery(MCCB), the Brief Psychiatric Rating Scale(BPRS), the Personal and Social Performance scale(PSP), and Schizophrenia Quality of Life Scale(SQLS). We further explored the effects of neurocognitive and social cognitive functions on their individual and social performance and quality of life in patients with schizophrenia. Results: (1) The scores of SQLS in the group with impaired social cognitive function were higher than those with good social function(101±46 vs 76±40, P=0.002). (2) The digital sequence and continuous performance test of the socially functional group were higher than the defect group. (3) There was a significant correlation between the years of education(R(2)=0.334, F=25.542), continuous performance (R(2)=0.316, F=35.647), BPRS (R(2)=0.280, F=60.386) and social function (P<0.001). (4) BPRS (R(2)=0.486, F=228.28), and emotional management (MSCEIT) (R(2)=0.510, F=124.789), education (R(2)=0.531, F=90.161), age (R(2)=0.539, F=69.644) significantly affected the SQLS score of patients with schizophrenia(P<0.001). Conclusion: The social function and quality of life of patients with schizophrenia are significantly correlated with their years of education and disease severity. Continuous performance in neurocognition significantly affects the social function of patients with schizophrenia, and emotional management in social cognition significantly affects their quality of life. Socially functional schizophrenia patients have higher digital sequences (working memory) and continuous performance (attention/alertness) scores.

Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data.

By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo. INTRODUCTION: No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups. METHODS: We searched different databases to select relevant studies. We performed Bayesian random effects network meta-analysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture. RESULTS: We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28-0.57), romosozumab (HR 0.49, 95% CI 0.29-0.75), risedronate (HR 0.62, 95% CI 0.50-0.79), zoledronate (HR 0.67, 95% CI 0.47-0.96), and alendronate (HR 0.69, 95% CI 0.47-0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33-0.92), romosozumab (HR 0.67, 95% CI 0.47-0.95), and denosumab (HR 0.68, 95% CI 0.50-0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4-2.6) and abaloparatide (RR 1.6, 95% CI 1.2-2.3). CONCLUSION: Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo.

Expression of Raptor and Rictor and their relationships with angiogenesis in colorectal cancer.

Mammalian target of rapamycin (mTOR) has two subtypes, i.e., mTORC1 and mTORC2, which contain the Raptor and Rictor core molecules, respectively. The effect of Raptor and Rictor on hypoxia inducible factor (HIF)-1α, HIF-2α, and vascular endothelial growth factor (VEGF) in colorectal cancer (CRC) is unclear. In this work, we investigated the correlations among Raptor, Rictor, HIF-1α, HIF-2α, and VEGF expression in CRC. We subsequently analyzed the clinicopathological features of patients. Immunohistochemistry, western blot, and RT-PCR analyses were performed to detect the expression of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in 120 cases of CRC and 60 cases of normal colorectal mucosa. CD34 was used to label microvascular density (MVD), which was found to be higher in patients with positive Raptor or Rictor than in those with negative Raptor or Rictor. The positive rates of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in CRC were significantly higher than in normal colorectal mucosa. Raptor expression was positively correlated with HIF-1α and VEGF but not with HIF-2α expression. By contrast, Rictor expression was positively correlated with HIF-2α and VEGF but not with HIF-1α expression. Survival analysis further indicated that Raptor, Rictor, HIF-1α, HIF-2α, VEGF and lymph node metastasis were independent prognostic factors in CRC. To conclude, Raptor and Rictor expression was related to the initiation and development of CRC and angiogenesis in different ways. The combined detection of Raptor and Rictor is important for patients with colorectal carcinoma in prognosis and optimal therapy.

[Bioinformatics analysis of severe emphysema genome microarray based on GEO database].

Objective: To investigate differential genes (DEGs) between no/mild and severe emphysema by bioinformatics analysis. Methods: The microarray dataset GSE1650, of lung tissue in no/mild and severe emphysema, was downloaded from the GEO database, and DEGs were obtained by t test. Analysis of DEGs based on DAVID database was used to obtain gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway. The protein-protein interaction network (PPI) was established using STRING database to identify hub genes. Results: A total of 76 DEGs were obtained, of which 62 genes were up-regulated and 14 genes were down-regulated in severe emphysema group. Gene ontology showed that the DEGs were mainly involved in neutrophil chemotaxis, cellular response to interleukin-1, extracellular matrix organization, immune response, and KEGG pathway involved cytokine-cytokine receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, platelet activation. Seventeen hub genes were recognized by PPI analysis, including CXCL8, RRAD, CLU, TIMP1, SEPP1, ISLR, BGN, COL1A1, COLIA2, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3 and TAGLN. Among them, fifteen genes (CLU, TIMP1, SEPP1, ISLR, BGN, COLIA2, COL1A1, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3, TAGLN) were up-regulated and two genes (CXCL8, RRAD) were down-regulated. Conclusion: Bioinformatics analysis based on GEO database showed that there were DEGs between non/mild and severe emphysema patients.