Ab Initio Density Functional Theory Calculation: Americium Hydrolysis Mechanism.

The hydrolysis mechanism of americium was calculated using density functional theory, and the detailed microscopic reaction mechanism was obtained. The results show that americium reacts with water along the octet state to produce oxides and H2, and that this reaction is exothermic. The interaction between Am and O atoms gradually changes from initially electrostatic interaction to covalent interaction, and continues to strengthen. During the reaction process, Am atoms always lose electrons, the 5f orbital is obviously involved, and there is df orbital hybridization. This study provides the necessary theoretical data support for the theoretical and experimental study of the actinide system.

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients.

OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC. RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients. RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs. CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.

Development of a convenient and effective hypertension risk prediction model and exploration of the relationship between Serum Ferritin and Hypertension Risk: a study based on NHANES 2017-March 2020.

Background: Hypertension is a major public health problem, and its resulting other cardiovascular diseases are the leading cause of death worldwide. In this study, we constructed a convenient and high-performance hypertension risk prediction model to assist in clinical diagnosis and explore other important influencing factors. Methods: We included 8,073 people from NHANES (2017-March 2020), using their 120 features to form the original dataset. After data pre-processing, we removed several redundant features through LASSO regression and correlation analysis. Thirteen commonly used machine learning methods were used to construct prediction models, and then, the methods with better performance were coupled with recursive feature elimination to determine the optimal feature subset. After data balancing through SMOTE, we integrated these better-performing learners to construct a fusion model based for predicting hypertension risk on stacking strategy. In addition, to explore the relationship between serum ferritin and the risk of hypertension, we performed a univariate analysis and divided it into four level groups (Q1 to Q4) by quartiles, with the lowest level group (Q1) as the reference, and performed multiple logistic regression analysis and trend analysis. Results: The optimal feature subsets were: age, BMI, waist, SBP, DBP, Cre, UACR, serum ferritin, HbA1C, and doctors recommend reducing salt intake. Compared to other machine learning models, the constructed fusion model showed better predictive performance with precision, accuracy, recall, F1 value and AUC of 0.871, 0.873, 0.871, 0.869 and 0.966, respectively. For the analysis of the relationship between serum ferritin and hypertension, after controlling for all co-variates, OR and 95% CI from Q2 to Q4, compared to Q1, were 1.396 (1.176-1.658), 1.499 (1.254-1.791), and 1.645 (1.360-1.989), respectively, with P < 0.01 and P for trend <0.001. Conclusion: The hypertension risk prediction model developed in this study is efficient in predicting hypertension with only 10 low-cost and easily accessible features, which is cost-effective in assisting clinical diagnosis. We also found a trend correlation between serum ferritin levels and the risk of hypertension.

Preliminary clinical study of personalized neoantigen vaccine therapy for microsatellite stability (MSS)-advanced colorectal cancer.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.

Aberrant Expression of Solute Carrier Family 35 Member A2 Correlates With Tumor Progression in Breast Cancer.

BACKGROUND/AIM: A recent study suggested that solute carrier family 35 member A2 (SLC35A2) is related to poor prognosis in patients with breast cancer. SLC35A2 transports uridine diphosphate-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi. MATERIALS AND METHODS: Immunohistochemical expression of SLC35A2 was evaluated using tissue microarrays. Cell growth, migration, and invasion of breast cancer cells were examined following loss- and gain-of-expression of SLC35A2. RESULTS: Normal breast tissue exhibited SLC35A2 immunoreactivity in the nucleus. A progressive increase in cytoplasmic expression from in situ carcinoma to invasive carcinoma was observed. There was a correlation between cytoplasmic SLC35A2 expression and breast cancer stage (p<0.001). MDA-MB-468 and MCF-7 cells transfected with SLC35A2 shRNA had unchanged cell viability but significantly reduced cell migration and invasion. In contrast, MDA-MB-231 and HCC1806 cells transfected with the SLC35A2 expression vector showed increased migration. CONCLUSION: Breast cancer progression is accompanied by differential expression patterns of SLC35A2. The migratory or invasive capacity of breast cancer cells is associated with SLC35A2 expression.

Accelerating L1-penalized expectation maximization algorithm for latent variable selection in multidimensional two-parameter logistic models.

One of the main concerns in multidimensional item response theory (MIRT) is to detect the relationship between observed items and latent traits, which is typically addressed by the exploratory analysis and factor rotation techniques. Recently, an EM-based L1-penalized log-likelihood method (EML1) is proposed as a vital alternative to factor rotation. Based on the observed test response data, EML1 can yield a sparse and interpretable estimate of the loading matrix. However, EML1 suffers from high computational burden. In this paper, we consider the coordinate descent algorithm to optimize a new weighted log-likelihood, and consequently propose an improved EML1 (IEML1) which is more than 30 times faster than EML1. The performance of IEML1 is evaluated through simulation studies and an application on a real data set related to the Eysenck Personality Questionnaire is used to demonstrate our methodologies.

FveARF2 negatively regulates fruit ripening and quality in strawberry.

Auxin response factors (ARFs) are transcription factors that play important roles in plants. ARF2 is a member of the ARF family and participates in many plant growth and developmental processes. However, the role of ARF2 in strawberry fruit quality remains unclear. In this study, FveARF2 was isolated from the woodland strawberry 'Ruegen' using reverse transcription-polymerase chain reaction (RT-PCR), which showed that FveARF2 expression levels were higher in the stem than in other organs of the 'Ruegen' strawberry. Moreover, FaARF2 was higher in the white fruit stage of cultivated strawberry fruit than in other stage. Subcellular localization analysis showed that FveARF2 is located in the nucleus, while transcriptional activation assays showed that FveARF2 inhibited transcription in yeast. Silencing FveARF2 in cultivated strawberry fruit revealed earlier coloration and higher soluble solid, sugar, and anthocyanin content in the transgenic fruit than in the control fruit, overexpression of FveARF2 in strawberry fruit delayed ripening and lower soluble solid, sugar, and anthocyanin content compared to the control fruit. Gene expression analysis indicated that the transcription levels of the fruit ripening genes FaSUT1, FaOMT, and FaCHS increased in FveARF2-RNAi fruit and decreased in FveARF2-OE fruit, when compared with the control. Furthermore, yeast one-hybrid (Y1H) and GUS activity experiments showed that FveARF2 can directly bind to the AuxRE (TGTCTC) element in the FaSUT1, FaOMT, and FaCHS promoters in vitro and in vivo. Potassium ion supplementation improved the quality of strawberry fruit, while silencing FveARF2 increased potassium ion content in transgenic fruit. The Y1H and GUS activity experiments also confirmed that FveARF2 could directly bind to the promoter of FveKT12, a potassium transporter gene, and inhibited its expression. Taken together, we found that FveARF2 can negatively regulate strawberry fruit ripening and quality, which provides new insight for further study of the molecular mechanism of strawberry fruit ripening.

Evaluation of circulating small extracellular vesicle-derived miRNAs as diagnostic biomarkers for differentiating between different pathological types of early lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. MicroRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested to be potential biomarkers for cancer diagnosis. The present study was designed to explore whether plasma-derived sEV miRNAs could be utilized as diagnostic biomarkers for differentiating between early-stage small cell lung cancer (SCLC) and early-stage non-small cell lung cancer (NSCLC). We compared the miRNA profiles of plasma-derived sEVs from healthy individuals, patients with early-stage SCLC and patients with early-stage NSCLC. Next-generation sequencing was used to screen for differentially expressed miRNAs (DEMs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the potential functions of these DEMs. Weighted gene coexpression network analysis (WGCNA) was used to identify the different pathology-related miRNA modules. We found that 22 DEMs were significantly different among healthy individuals, patients with early-stage SCLC, and patients with early-stage NSCLC. We selected six representative DEMs for validation by qRT‒PCR, which confirmed that miRNA-483-3p derived from plasma sEVs could be used as a potential biomarker for the diagnosis of early-stage SCLC, miRNA-152-3p and miRNA-1277-5p could be used for the diagnosis of early-stage NSCLC respectively.

The vibrational and hyperfine spectroscopy toward laser cooling 87Sr35Cl.

We theoretically investigate the possibility of laser cooling 87Sr35Cl molecule in accordance with vibrational and hyperfine spectroscopy. The potential energy curves and dipole moment of the X2Σ+1/2, A2Π1/2,3/2 and B2Σ+ states are calculated using ab initio method and the spectroscopic parameters are in good agreement with the experimental data. On account of the accurate potential energy curves and the transition dipole moment, the Franck - Condon factors and radiative lifetimes are predicted. Comparing the conditions of laser cooling candidate molecules, the A2Π 1/2 â†” X2Σ+1/2 transition is selected as the laser cooling cycle system. In order to obtain an approximately closed cooling cycle system, we employed matrix element algorithm to calculated the hyperfine spectroscopy and branching ratios of the 87Sr35Cl molecule. Furthermore, an electro-optical modulator (EOM) is designed including six hyperfine levels of the ground state X2Σ+1/2 (v = 0, N = 1).

[Effect of wheat-grain moxibustion on the expression of Beclin-1/GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy].

OBJECTIVE: To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR. METHODS: A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope. RESULTS: After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups. CONCLUSION: Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.

Direct moxibustion exerts an analgesic effect on cervical spondylotic radiculopathy by increasing autophagy via the Act A/Smads signaling pathway.

BACKGROUND: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. METHODS: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR. RESULTS: DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons. CONCLUSION: DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.

Girdin influences pancreatic cancer progression by regulating c-MYC expression.

Pancreatic ductal adenocarcinoma is a complex gastrointestinal tumor with high metastatic potential and poor prognosis. Actin-binding protein Girdin is highly expressed in a variety of tumors and promotes tumorigenesis and progression. However, the mechanisms underlying the involvement of Girdin in pancreatic cancer have not been clarified. In this study, we observed that the expression of Girdin was upregulated in pancreatic cancer cells. The siRNA-mediated gene knockdown experiments showed that reduced expression of Girdin in pancreatic cancer cells inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. Functional assays revealed that c-MYC overexpression in pancreatic cancer cells could significantly increase the cell proliferation ability and rates of cell migration and invasion while decreasing the apoptosis rate. It has been shown that phosphorylation plays a role in the functional regulation of the c-MYC gene. Subsequently, we examined the expression level of c-MYC in cells with manipulated expression of Girdin and identified a positive correlation between Girdin expression and c-MYC expression. Moreover, we found that Girdin knockdown in c-MYC-overexpressing pancreatic cancer cells slowed cell growth, blocked the cell cycle progression, significantly promoted apoptosis, and markedly decreased the cell migration and invasion. This finding indicated that silencing Girdin could mitigate the effect of c-MYC on promoting proliferation and metastasis of pancreatic cancer. Overall, this study provided evidence that Girdin promoted pancreatic cancer development presumably by regulating the c-MYC overexpression.

Latent variable sdelection in multidimensional item response theory models using the expectation model selection algorithm.

The aim of latent variable selection in multidimensional item response theory (MIRT) models is to identify latent traits probed by test items of a multidimensional test. In this paper the expectation model selection (EMS) algorithm proposed by Jiang et al. (2015) is applied to minimize the Bayesian information criterion (BIC) for latent variable selection in MIRT models with a known number of latent traits. Under mild assumptions, we prove the numerical convergence of the EMS algorithm for model selection by minimizing the BIC of observed data in the presence of missing data. For the identification of MIRT models, we assume that the variances of all latent traits are unity and each latent trait has an item that is only related to it. Under this identifiability assumption, the convergence of the EMS algorithm for latent variable selection in the multidimensional two-parameter logistic (M2PL) models can be verified. We give an efficient implementation of the EMS for the M2PL models. Simulation studies show that the EMS outperforms the EM-based L1 regularization in terms of correctly selected latent variables and computation time. The EMS algorithm is applied to a real data set related to the Eysenck Personality Questionnaire.

[Observation on clinical effect of acupuncture combined with wheat-grain moxibustion for mild to moderate postpartum depression].

OBJECTIVE: To compare the clinical effect of acupuncture combined with wheat-grain moxibustion and oral sertraline hydrochloride dispersible tablets in the treatment of mild to moderate postpartum depression. METHODS: Sixty patients with mild to moderate postpartum depression were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with psychotherapy. The control group was treated with oral sertraline hydrochloride dispersible tablets, 50 mg each time, once a day; the observation group was treated with acupuncture at Qihai (CV 6), Zusanli (ST 36), Xuehai (SP 10), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3), etc. combined with wheat-grain moxibustion at Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), once every other day, 3 times a week. Both groups were treated for 4 weeks as a course, with 2 consecutive courses of treatment. Before and after treatment and follow-up of 3 months after the end of treatment, the Hamilton depression scale (HAMD), Edinburgh postnatal depression scale (EPDS) and World Health Organization quality of life-BREF (WHOQOL-BREF) score of the two groups were compared, and the clinical effect was assessed. RESULTS: After treatment and during follow-up, the HAMD and EPDS scores of the two groups were lower than before treatment (P<0.05), and the WHOQOL-BREF scores of the two groups were higher than before treatment (P<0.05). In the control group, the scores of HAMD and EPDS during follow-up were higher than after treatment (P<0.05), and the score of WHOQOL-BREF during follow-up was lower than after treatment (P<0.05). After treatment and during follow-up, the HAMD and EPDS scores of the observation group were lower than those of the control group (P<0.05), and the WHOQOL-BREF score of the observation group was higher than that of the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), which was higher than 86.7% (26/30) of the control group (P<0.05). CONCLUSION: Acupuncture combined with wheat-grain moxibustion can improve the depressive symptoms of patients with mild to moderate postpartum depression and improve their quality of life, and the clinical effect is more lasting and stable than oral sertraline hydrochloride dispersible tablets.

Protective effect of LIF-huMSCs on the retina of diabetic model rats.

AIM: To investigate the protective effect of human umbilical cord mesenchymal stem cells (hUCMSCs) modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism. METHODS: A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor (LIF) was constructed. Overexpression was verified by fluorescent quantitative polymerase chain reaction (qPCR). Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group (group A), streptozotocin-induced diabetic control group (group B), diabetic rats at 3mo injected with empty vector-transfected hUCMSCs (group C) or injected with LIF-hUCMSCs (group D). Four weeks after the intravitreal injection, analyses in all groups included retinal function using flash electroretinogram (F-ERG), retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran (FITC-dextran), and retinal structure examination of sections using hematoxylin and eosin staining. Expression levels of adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP), and neurotrophin-4 (NT-4) in each group was detected using immunohistochemistry, PCR, Western blotting, and ELISA, respectively. RESULTS: A stable transgenic cell line of LIF-hUCMSCs was constructed. F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A, severe damage of the retinal blood vessels and function in group B, and improved retinal structure and function in group C and especially group D. qPCR, ELISA, and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B, C, and D than in group A. hs-CRP expression was significantly higher in group B than in groups A, C, and D, and was significantly higher in group C than in group D (P<0.05). CONCLUSION: LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

Cognitive Diagnosis Modeling Incorporating Item-Level Missing Data Mechanism.

The aim of cognitive diagnosis is to classify respondents' mastery status of latent attributes from their responses on multiple items. Since respondents may answer some but not all items, item-level missing data often occur. Even if the primary interest is to provide diagnostic classification of respondents, misspecification of missing data mechanism may lead to biased conclusions. This paper proposes a joint cognitive diagnosis modeling of item responses and item-level missing data mechanism. A Bayesian Markov chain Monte Carlo (MCMC) method is developed for model parameter estimation. Our simulation studies examine the parameter recovery under different missing data mechanisms. The parameters could be recovered well with correct use of missing data mechanism for model fit, and missing that is not at random is less sensitive to incorrect use. The Program for International Student Assessment (PISA) 2015 computer-based mathematics data are applied to demonstrate the practical value of the proposed method.

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection.

AIM: To explore the efficacy of minimally invasive vitrectomy (MIV) with or without internal limiting membrane (ILM) peeling on the treatment of diabetic macular edema (DME) in proliferative diabetic retinopathy (PDR) combining with preoperative anti-vascular endothelial growth factor (anti-VEGF) injection. METHODS: Totally 132 eyes (132 patients) diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye Hospital. The single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 eyes. Anti-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to 3y. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), total macular volume (TMV), macular edema (ME) severity, intraocular pressure (IOP), and complications were recorded. Prognostic factors of visual acuity following ILM peeling were analyzed. RESULTS: The BCVA was higher than preoperative values at 1, 3, 6, and 12mo after surgery in both groups (all P<0.05). At 6 and 12mo, the BCVA of the combined group was significantly higher than that of the MIV only group (0.52±0.23 vs 0.64±0.29 logMAR, P=0.011 in 6mo; 0.41±0.25 vs 0.52±0.25 logMAR, P=0.008 in 12mo). Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1st month (1mo 397.65±106.18 vs 451.94±118.88 µm in MIV only group; 388.88±108.68 vs 464.36±111.53 µm in combined group; both P<0.05) and decreased gradually. The differences between the two groups were statistically significant at 3, 6, and 12mo (P=0.004, 0.003, 0.00 respectively). The TMV was decreased from the 3rd month in the single treatment group (3mo 11.14±1.66 vs 12.20±2.09 mm3, P<0.05). At 12mo, the proportion of eyes with edema that had CRT more than 350 µm was significantly lower than before surgery (13.24% vs 77.94% in MIV only group; 1.56% vs 81.25% in combined group; both P<0.05). There was no significant difference in the recurrence incidence of macular epiretinal membrane, ME, transient IOP increase, vitreous rebleeding, or traction retinal detachment between the two groups. BCVA after ILM excision was positively correlated with the CRT and ME degree before and after surgery (r=0.430, 0.485, respectively; P<0.05). CONCLUSION: MIV combined with ILM peeling accelerates the absorption of ME, improves vision, reduces the postoperative CRT and TMV, and reduces the recurrence rate of postoperative ME.

Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed. MATERIALS AND METHODS: The "compound-target-cell-disease" network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model. RESULTS: Through the "compound-target-cell-disease" network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3'-O-gallate, torachrysone-8-O-beta-D-(6'-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB. CONCLUSIONS: This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism.

Simultaneous expression of two pathogenic genes in four Chinese patients affected with inherited retinal dystrophy.

AIM: To describe the complex, overlapping phenotype of four Chinese patients with inherited retinal dystrophies (IRDs) who harbored two pathogenic genes simultaneously. METHODS: This retrospective study included 4 patients affected with IRDs. Medical and ophthalmic histories were obtained, and clinical examinations were performed. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) based on exome capture technology was used for genetic screening. RESULTS: Four patients were identified to harbor disease-causing variants in two different genes. Patient retinitis pigmentosa (RP) 01-II:1 exhibited both classical ABCA4-induced Stargardt disease (STGD) 1 and USH2A-associated RP, patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP, patient RP03-II:1 exhibited both USH2A-induced autosomal recessive retinitis pigmentosa (arRP) syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa (adRP), and patient RP04-II:2 exhibited USH2A-induced arRP syndrome and EYS-induced arRP at the same time. CONCLUSION: Our study demonstrates that genotype-phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.

Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation.

Perturbed Nicotinamide adenine dinucleotide (NAD+) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD+ generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Knockdown of QPRT expression inhibited breast cancer cell migration and invasion. Consistently, ectopic expression of QPRT promoted cell migration and invasion in breast cancer cells. Treatment with QPRT inhibitor (phthalic acid) or P2Y11 antagonist (NF340) could reverse the QPRT-induced invasiveness and phosphorylation of myosin light chain. Similar reversibility could be observed following treatment with Rho inhibitor (Y16), ROCK inhibitor (Y27632), PLC inhibitor (U73122), or MLCK inhibitor (ML7). Altogether, these results indicate that QPRT enhanced breast cancer invasiveness probably through purinergic signaling and might be a potential prognostic indicator and therapeutic target in breast cancer.