Structure-inclusive similarity based directed GNN: a method that can control information flow to predict drug-target binding affinity.

MOTIVATION: Exploring the association between drugs and targets is essential for drug discovery and repurposing. Comparing with the traditional methods that regard the exploration as a binary classification task, predicting the drug-target binding affinity can provide more specific information. Many studies work based on the assumption that similar drugs may interact with the same target. These methods constructed a symmetric graph according to the undirected drug similarity or target similarity. Although these similarities can measure the difference between two molecules, it is unable to analyze the inclusion relationship of their substructure. For example, if drug A contains all the substructures of drug B, then in the message-passing mechanism of the graph neural network, drug A should acquire all the properties of drug B, while drug B should only obtain some of the properties of A. RESULTS: To this end, we proposed a structure-inclusive similarity (SIS) which measures the similarity of two drugs by considering the inclusion relationship of their substructures. Based on SIS, we constructed a drug graph and a target graph, respectively, and predicted the binding affinities between drugs and targets by a graph convolutional network-based model. Experimental results show that considering the inclusion relationship of the substructure of two molecules can effectively improve the accuracy of the prediction model. The performance of our SIS-based prediction method outperforms several state-of-the-art methods for drug-target binding affinity prediction. The case studies demonstrate that our model is a practical tool to predict the binding affinity between drugs and targets. AVAILABILITY AND IMPLEMENTATION: Source codes and data are available at https://github.com/HuangStomach/SISDTA.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.

AIM: To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students. METHODS: Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University. Their data were used to identify the different types of accommodation and non-strabismic binocular vision dysfunction and to determine their frequency. Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities. RESULTS: The results showed that 36.71% of the subjects had accommodation and non-strabismic binocular vision issues, with 8.86% being attributed to accommodation dysfunction and 27.85% to binocular abnormalities. Convergence insufficiency (CI) was the most common abnormality, accounting for 13.29%. Those with these abnormalities experienced higher levels of eyestrain (χ2=69.518, P<0.001). The linear correlations were observed between the difference of binocular spherical equivalent (SE) and the index of horizontal esotropia at a distance (r=0.231, P=0.004) and the asthenopia survey scale (ASS) score (r=0.346, P<0.001). Furthermore, the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range (r=-0.321, P<0.001), the convergence of negative fusion images at close range (r=-0.294, P<0.001), the vergence facility (VF; r=-0.234, P=0.003), and the set of negative fusion images at far range (r=-0.237, P=0.003). Logistic regression analysis indicated that gender, age, and the difference in right and binocular SE did not influence the emergence of these abnormalities. CONCLUSION: Binocular vision abnormalities are more prevalent than accommodation dysfunction, with CI being the most frequent type. Greater binocular refractive disparity leads to more severe eyestrain symptoms.

Outcomes of allogeneic hematopoietic stem cell transplantation in R/R DLBCL patients with failure of CAR-T therapy.

From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27-52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31-370) days. The median follow-up was 21 (3-69) months. 5/10 patients attained CR and 1/10 patient attained PR during the follow up. The objective response rate (ORR) was 60%. The 1-year overall survival (OS) and progression-free survival (PFS) were 70% and 40%, respectively. At the time of the analysis, 6 patients were still living. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). Non-relapse was 20.0%.

HLA-targeted sequencing reveals the pathogenic role of HLA-B*15:02/HLA-B*13:01 in albendazole-induced liver failure: a case report and a review of the literature.

Drug-induced liver injury (DILI) is one of the serious adverse drug reactions (ADRs), which belongs to immune-mediated adverse drug reactions (IM-ADRs). As an essential health drug, albendazole has rarely been reported to cause serious liver damage. A young man in his 30 s developed severe jaundice, abnormal transaminases, and poor blood coagulation mechanism after taking albendazole, and eventually developed into severe liver failure. The patient was found heterozygous of HLA-B*15:02 and HLA-B*13:01 through HLA-targeted sequencing, which may have a pathogenic role in the disease. This case report summarizes his presentation, treatment, and prognosis. A useful summary of the diagnosis and associated genetic variant information is provided.

Analysis of independent risk factors for acute acquired comitant esotropia.

AIM: To explore the risk factors for acute acquired comitant esotropia (AACE). METHODS: A retrospective cohort study was conducted by analyzing 83 patients (case group) with AACE who underwent strabismus correction surgery from January 1, 2021 to June 30, 2022. Totally 73 outpatient volunteers were recruited during the same period as the normal control group. The case group's binocular vision time, near and distance esotropia angle, and near stereo vision function were recorded, and the age, gender, refractive status, and best-corrected visual acuity (BCVA) of both groups were analyzed. Additionally, multiple logistic regression analysis was conducted using an eye usage condition questionnaire to determine the independent risk factors for AACE. RESULTS: In the case group, 61 patients (73.49%) had myopia, with a mean equivalent spherical power (SE) of -3.35±3.31 D (range: +2.75 to -10.62 D) of the right eye and -2.87±3.35 D (range: +2.75 to -11.12 D) of the left eye. The average duration of diplopia in the case group was 29.83±35.72mo, of which 80 patients (96.39%) were primarily with distance diplopia. The near and distance esotropia angle after wearing glasses were 52.36±20.95 prism degree (PD) and 56.71±19.54 PD, respectively, and there was no statistically significant difference between the two (t=1.38, P=0.169). The incidence of improper glasses wearing and unhealthy eye habits in the case group was significantly higher than those in the control group (P<0.05). Close-up work without glasses [ß=2.30, odds ratio (OR)=10, 95% confidence interval (CI) 2.35-42.51, P=0.002] and near work in supine position (ß=1.80, OR=6.02, 95%CI 3.29-11.02, P<0.001) were independent risk factors for AACE. CONCLUSION: Patients with AACE mainly present with distance diplopia, and there is a high degree of variation in myopia. Near work without wearing glasses and in supine position are independent risk factors for AACE.

ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner.

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most aggressive cancers and is notorious for its extremely poor prognosis. However, very few molecular biological studies have been performed. As a novel method of epigenetic gene modulation, N6-methyladenosine (m6A) RNA modification occurs in HPSCC. The expression of the m6A demethylase AlkB homolog 5 (ALKBH5) is frequently downregulated in human HPSCC. Furthermore, we found that ALKBH5 impaired cell proliferation by regulating human Toll-like receptor 2 (TLR2) in an m6A-dependent manner in HPSCC cells. ALKBH5 decreased TLR2 m6A modification, which could be recognized by the m6A readers IGF2BP2 and YTHDF1. IGF2BP2 facilitates TLR2 mRNA stability, whereas YTHDF1 promotes TLR2 mRNA translation. The current work uncovered a critical function of ALKBH5 in TLR2 regulation and provides a novel role for m6A demethylation of mRNA in HPSCC. The inhibition of m6A modification of ALKBH5 in HPSCC deserves further clinical investigation.

A Deep Neural Network-Based Co-Coding Method to Predict Drug-Protein Interactions by Analyzing the Feature Consistency Between Drugs and Proteins.

Exploring drug-protein interactions (DPIs) through computational methods can effectively reduce the workload and the cost of DPI identification. Previous works try to predict DPIs by integrating and analyzing the unique features of drugs and proteins. They cannot adequately analyze the consistency between the drug features and the protein features due to their different semantics. However, the consistency of their features, such as the correlation originating from their sharing diseases, may reveal some potential DPIs. Here we propose a deep neural network-based co-coding method (DNNCC for short) to predict novel DPIs. DNNCC projects the original features of drugs and proteins to a common embedding space through a co-coding strategy. In this way, the embedding features of drugs and proteins have the same semantics. Therefore, the prediction module can discover the unknown DPIs by exploring the feature consistency between drugs and proteins. The experimental results indicate that the performance of DNNCC is significantly superior to five state-of-the-art DPI prediction methods under several evaluation metrics. The superiority of integrating and analyzing the common features of drugs and proteins is proved by the ablation experiments. The novel DPIs predicted by DNNCC verify that DNNCC is a powerful prior tool that can effectively discover potential DPIs.

Venetoclax-based combination therapy in R/R DLBCL patients with failure of CAR-T therapy.

There are few effective therapeutic options available for R/R DLBCL patients who have undergone CAR-T therapy. We retrospectively assessed 10 R/R DLBCL patients with complete clinical records who received venetoclax-based combination therapy following CAR-T therapy failed in our center between July 2020 and December 2021. After receiving CAR-T therapy, they all relapsed within a few months. As salvage regimens, they were all given venetoclax-based combination therapy. The objective response rate (ORR) was 80 percent, and the complete response rate was 30 percent. At the time of the analysis, 7 patients were still living. Our research has demonstrated that venetoclax-based combination treatment for R/R DLBCL patients who failed CAR-T therapy has a high effectiveness and manageable toxicity.

Drug-Protein interaction prediction by correcting the effect of incomplete information in heterogeneous information.

MOTIVATION: Large-scale heterogeneous data provide diverse perspectives for predicting drug-protein interactions (DPIs). However, the available information on molecular interactions and clinical associations related to drugs or proteins is incomplete because there may be unproven interactions and associations. This incomplete information in the available data is presented in the form of non-interaction and non-correlation, which may mislead the prediction model. Existing methods fuse incomplete and complete information without considering their integrity, so the negative effects of incomplete information still exist. RESULTS: We develop a network-based DPI prediction method named BRWCP, which uses the complete information network to correct the prediction results acquired by the incomplete information network. By integrating relevant heterogeneous information that may be incomplete, the feature similarities of drugs and proteins are obtained. Combining the feature similarities and known DPIs, an incomplete information-based drug-protein heterogeneous network is constructed. Then, a bidirectional random walk with pruning algorithm is adopted in this heterogeneous network to predict potential DPIs. Next, the predicted DPIs are combined with the chemical fingerprint similarity of drugs and amino acid sequence similarity of proteins to construct the complete information network. The bidirectional random walk with pruning algorithm is applied in the new network to obtain the final prediction results until it converges. Experimental results show that BRWCP is superior to several state-of-the-art DPI prediction methods, and case studies further confirm its ability to tap potential DPIs. AVAILABILITY AND IMPLEMENTATION: The code and data used in BRWCP are available at https://github.com/lyfdomain/BRWCP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CPMCP: a database of Chinese patent medicine and compound prescription.

Although several traditional Chinese medicine (TCM)-related databases have emerged, they focus on researching single medicinal materials, which is far from sufficient for clinical research and application. In comparison, compound prescriptions are more informative and meaningful in TCM, for they embody the information on the compatibility of TCM besides the relatively isolated information about single medicinal materials. The compatibility information is essential in TCM because it conveys not only what components are involved to treat special diseases but also how to combine these single medical materials. We established a database of Chinese patent medicine and compound prescription (CPMCP). It demonstrates the prescription information of Chinese patent medicines (CPMs) and ancient Chinese medicine prescriptions (CMPs). CPMCP reports their comprehensive and standardized information such as the components, indications and contraindications. It is worth mentioning that we organized relevant experts and spent lots of time manually mapping the functions of compound prescriptions in ancient Chinese to the standardized TCM symptom vocabularies, obtaining a total of 71 414 associations between compound prescriptions and TCM symptoms. In this way, CPMCP established the associations between TCM and modern medicine (MM) according to the associations between TCM symptoms and MM symptoms. In addition, to further exhibit the compatibility mechanism of compound prescriptions, CPMCP summarizes a set of common drug combination principles by analyzing the existing prescriptions. We believe that CPMCP can promote the modernization of TCM and make greater contributions to MM. Database URL http://cpmcp.top.

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration. METHODS: We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples. RESULTS: We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module 'cyan', TARS in the module 'darkorange', and COPB2 and RYK in the module 'lightyellow' showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients. CONCLUSIONS: Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes.

Multi-variable AUC for sifting complementary features and its biomedical application.

Although sifting functional genes has been discussed for years, traditional selection methods tend to be ineffective in capturing potential specific genes. First, typical methods focus on finding features (genes) relevant to class while irrelevant to each other. However, the features that can offer rich discriminative information are more likely to be the complementary ones. Next, almost all existing methods assess feature relations in pairs, yielding an inaccurate local estimation and lacking a global exploration. In this paper, we introduce multi-variable Area Under the receiver operating characteristic Curve (AUC) to globally evaluate the complementarity among features by employing Area Above the receiver operating characteristic Curve (AAC). Due to AAC, the class-relevant information newly provided by a candidate feature and that preserved by the selected features can be achieved beyond pairwise computation. Furthermore, we propose an AAC-based feature selection algorithm, named Multi-variable AUC-based Combined Features Complementarity, to screen discriminative complementary feature combinations. Extensive experiments on public datasets demonstrate the effectiveness of the proposed approach. Besides, we provide a gene set about prostate cancer and discuss its potential biological significance from the machine learning aspect and based on the existing biomedical findings of some individual genes.

Autoencoder-based drug-target interaction prediction by preserving the consistency of chemical properties and functions of drugs.

MOTIVATION: Exploring the potential drug-target interactions (DTIs) is a key step in drug discovery and repurposing. In recent years, predicting the probable DTIs through computational methods has gradually become a research hot spot. However, most of the previous studies failed to judiciously take into account the consistency between the chemical properties of drug and its functions. The changes of these relationships may lead to a severely negative effect on the prediction of DTIs. RESULTS: We propose an autoencoder-based method, AEFS, under spatial consistency constraints to predict DTIs. A heterogeneous network is established to integrate the information of drugs, proteins and diseases. The original drug features are projected to an embedding (protein) space by a multi-layer encoder, and further projected into label (disease) space by a decoder. In this process, the clinical information of drugs is introduced to assist the DTI prediction. By maintaining the distribution of drug correlation in the original feature, embedding and label space, AEFS keeps the consistency between chemical properties and functions of drugs. Experimental comparisons indicate that AEFS is more robust for imbalanced data and of significantly superior performance in DTI prediction. Case studies further confirm its ability to mine the latent DTIs. AVAILABILITY AND IMPLEMENTATION: The code of AEFS is available at https://github.com/JackieSun818/AEFS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation.

BACKGROUND: Refractory otomycosis is a common condition that is difficult to treat. OBJECTIVES: This study aimed to evaluate the effectiveness of 1% topical voriconazole drops in the treatment of otomycosis. METHODS: This retrospective analysis was conducted from November 2017 to November 2019. Patients who had refractory otomycosis without tympanic membrane perforation confirmed by microbial culture and fluorescent staining were included in the study. All patients were treated with 1% topical voriconazole drops hourly at daytime for 2 weeks. Evaluation of effectiveness was conducted 1 month after the completion of topical voriconazole treatment. Before and after topical voriconazole treatment, hearing tests were performed in all patients. RESULTS: Fifty-five patients were included in this study. The reasons for refractoriness were resistant recurrence to imidazole drugs (50 cases, 90.9%) and difficulty in cleaning the external auditory canal (5 cases, 9.1%). The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), Aspergillus niger (10.9%), and Aspergillus fumigatus (9.1%). After 2 weeks of treatment with 1% topical voriconazole drops, otomycosis in all patients was resolved. There was no significant change in bone conduction before and after topical voriconazole treatment (paired t-test, P = 0.5023; linear correlation analysis, R2 = 0.98; equation, y = 1.003x-0.284). Adverse effects, such as blurred vision and phototoxicity, were not observed in any patient. CONCLUSIONS: Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation within 2 weeks.

[Responses of photosynthetic physiology and sap flow to the introduction of external dye in Populus ×euramericana cv. '74/76']. / 107æ¨å ‰åˆç”Ÿç†ä¸Žæ ‘å¹²æ¶²æµå¯¹å¤–æºæŸ“æ¶²å¯¼å ¥çš„å“åº”.

The exogenous liquid introduction technology is an effective way to produce the value-added poplar wood with excellent pattern color. This technology was used to add the various concentrated active red dyeing solution (0.2%, 0.4% and 0.6%) into target trees of six-year-old 107 poplar (Populus ×euramericana cv. '74/76'). The photosynthetic gas exchange parameter and sap flow rate were measured by Li-6400 photosynthetic instrument and TDP stem flowmeter, respectively. We analyzed the relationship between photosynthetic parameters, sap flow rate and dye absorption, and the effects of exogenous dye solution on the photosynthetic physiology and sap flow characteristics. The results showed that exogenous dyeing solution significantly inhibited flow rate of poplar trunks. The 0.2% concentrated liquid was far less effective than others (0.4% and 0.6%). The net photosynthetic rate (Pn), stomatal conductance (gs) and transpiration rate (Tr) of poplars treated with different concentrated dyeing liquids were significantly lower than the control poplar. The intercellular carbon dioxide concentration (Ci) decreased first and then increased. The inhibitory effects of 0.4% and 0.2% concentrated dyeing solutions on photosynthesis were stronger than that of 0.6%. Dye absorption decreased with increasing dye concentration. The maximum liquid flow rate, Pn, gs and Tr were significantly negatively correlated with the dye content. The contents of chlorophyll (a+b), chlorophyll a and chlorophyll b in exogenous dyeing solution treatments were significantly lower than those of the control at the later stage. The concentration of dyeing solution and introduction time determined the amount of dye absorption. The dye solution 0.4%, which was introduced for three days, could ensure the appropriate dye absorption and reduce the inhibitory effect on the physiological activities of the poplar.

The effect of the standard length of the first prescription on the adherence to sublingual immunotherapy for patients with allergic rhinitis.

BACKGROUND: Poor adherence to sublingual immunotherapy (SLIT) has become a major cause of unsatisfactory clinical efficacy for patients with allergic rhinitis (AR). This study was designed to identify the effect of different first prescription lengths on the adherence to SLIT. METHODS: The clinical data of 306 patients with AR who started SLIT between January 2017 and June 2018 were retrospectively reviewed. Patients were divided into 3 groups according to the length of their first prescription (group A: less than 3 months, group B: 3 to 6 months, group C: more than 6 months). The numbers of adherent or nonadherent patients in each group and the main reasons of nonadherence were analyzed. RESULTS: Groups A, B, and C included 102, 161, and 43 patients, respectively. The average lengths of the first prescription for group A, B, and C were 62.52 ± 17.63, 102.21 ± 9.22, and 189.07 ± 17.97 days. There were significance differences among the 3 groups (p < 0.05). There were 42 (41.18%), 112 (69.57%), and 37 (86.05%) adherent patients in group A, B, and C. There were 60 (58.82%), 49 (30.43%), and 6 (13.95%) nonadherent patients in group A, B, and C. There were significant differences in the proportions of adherent and nonadherent patients among the 3 groups (p < 0.05). The following reasons were cited for nonadherence to SLIT: the long course of SLIT; inconvenience of getting the prescription; ineffectiveness; side effects; and other reasons. CONCLUSION: Under certain conditions, 6 months is recommended as the standard length for the first prescription, which can significantly improve adherence to SLIT in patients with AR.

Two new NiII and ZnII metal-organic frameworks of glutarate and 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene ligands: syntheses, structures and luminescence sensing properties.

Two new metal-organic frameworks (MOFs), namely, three-dimensional poly[diaquabis{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}bis(µ2-glutarato)dinickel(II)] monohydrate], {[Ni2(C5H6O4)2(C16H18N4)2(H2O)2]·H2O}n or {[Ni2(Glu)2(1,4-mbix)2(H2O)2]·H2O}n, (I), and two-dimensional poly[[{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}(µ2-glutarato)zinc(II)] tetrahydrate], {[Zn(C5H6O4)(C16H18N4)]·4H2O}n or {[Zn(Glu)(1,4-mbix)]·4H2O}n (II), have been synthesized hydrothermally using glutarate (Glu2-) mixed with 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene (1,4-mbix), and characterized by single-crystal X-ray diffraction, IR and UV-Vis spectroscopy, powder X-ray diffraction, and thermogravimetric and photoluminescence analyses. NiII MOF (I) shows a 4-connected 3D framework with point symbol 66, but is not a typical dia network. ZnII MOF (II) displays a two-dimensional 44-sql network with one-dimensional water chains penetrating the grids along the c direction. The solid-state photoluminescence analysis of (II) was performed at room temperature and the MOF exhibits highly selective sensing toward Fe3+ and Cr2O72- ions in aqueous solution.

Cerumen impaction was composed of abnormal exfoliation of keratinocytes that was correlated with infection.

OBJECTIVE: This study investigated the exact composition and tried to be helpful in explaining the etiologic mechanism of cerumen impaction in the external auditory canal (EAC). METHODS: A hundred impacted cerumen samples and 15 normal cerumen samples were collected by manual removal and divided into 2 groups. All samples were examined via microbial culture, hematoxylin-eosin staining, periodic acid-Schiff staining, and fungal fluorescent staining. RESULTS: Eighty-eight patients in group 1 were in the habit of using cotton buds. Forty-seven impacted cerumen samples tested positive for microbes, while only 1 sample of normal cerumen tested positive for microbes (p < .05). The most commonly isolated bacterium and fungus was Staphylococcus aureus and Aspergillus terreus respectively. All cerumen samples were composed of exfoliated keratinocytes and microorganisms assessed via pathologic examination. However, unlike normal cerumen, impacted cerumen contained nucleated keratinocytes and infiltrated neutrophils. Recurrent impaction was found only among patients who tested mold culture-positive. CONCLUSION: Impacted cerumen is composed of abnormal exfoliated keratinocytes that was correlated with microbial-induced neutrophil-mediated inflammation. Mold infection is highly correlated with recurrent cerumen impaction. Microbial culture of removed impacted cerumen is strongly recommended. Ear cleaning with cotton buds, particularly when the EAC is wet might be one of the important causes of cerumen impaction which is need further studied. LEVEL OF EVIDENCE: 2b.

LINC00205 modulates the expression of EPHX1 through the inhibition of miR-184 in hepatocellular carcinoma as a ceRNA.

Several studies have shown that low expression of epoxide hydrolase 1 (EPHX1) is closely associated with varying human cancers, including hepatocellular carcinoma (HCC). This study aims to explore the potential mechanism of EPHX1 silencing and revealed a novel regulatory pathway in the pathogenesis of HCC. In this study, micro ribonucleic acid (miR)-184 was predicted and validated to be a regulator of EPHX1 through experiments, and its expression was negatively correlated with the messenger RNA (mRNA) levels of EPHX1 in primary tumors. Elevation of EPHX1 suppressed cell proliferation and migration as well as cell cycle progression, and induced apoptosis, while downregulation of miR-184 exhibited the opposite effect on cellular processes. Moreover, LINC00205 interacted with miR-184 and was markedly downregulated in tumors. The effects of the miR-184 inhibitor on cell proliferation, apoptosis, and migration were reversed in part by the transfection with LINC00205 small interfering RNAs. In addition, LINC00205 acted as a molecular sponge to positively regulate the mRNA and protein levels of EPHX1 via regulating miR-184. The tumorigenicity of HCC cells was enhanced by LINC00205 shRNA but diminished by overexpression of EPHX1 in vivo. Clinically, the EPHX1 expression in patients with HCC was markedly downregulated. Taken together, the results of this study suggest that as a competing endogenous RNA, LINC00205 may regulate EPHX1 by inhibiting miR-184 in the progression of HCC and that targeting the LINC00205/miR-184/EPHX1 axis may provide a treatment protocol for patients.

[Analysis of Curative Efficacy of Different Chemotherapy Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation on Multiple Myeloma].

OBJECTIVE: To evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) on patients with multiple myeloma( MM) after Sequential different chemotherapy. METHODS: Seven cases of patients with MM were included in the A group, and 14 cases of patients received 4-6 courses of chemotherapy with VAD and MP before transplantation were included in the B group and received 4-6 courses of chemotherapy with VTD and VD before transplantation. Auto-peripheral blood hematopoietic stem cell were mobilized by G-CSF. Condition regimen were melphalan(A group) or bortezomib combined melphalan(B group). IFN-α(A group) or Thalidomide(B group) was used as maintenance treatment after auto-PBHSCT. RESULTS: Two cases of patients reached to complete remission (CR)(2/7,28.6%),1 case got very good partial remission (VGPR) (1/7,14.3%), 4 cases got partial remission(PR) (4/7,57.1%) in A group, and 9 cases got CR (9/14,64.3%), 3 cases got VGPR(3/14,21.4%), and 2 cases got PR(2/14,14.3%) in the B group before auto-PBHSCT. The CR and VGPR were significant difference between 2 groups (P<0.05). All the patients got hematopoietic recovery. In 2 groups, the median time of ANC recovery≥0.5×109/L was 13 (11-16) and 14（11-18）days, that of WBC recovery ≥4.0×109/L were 16(15-19) and 18(16-20)days, Plt recovery ≥ 50 ×109/L was 21 (18-25) and 21(17-25) days. Bone marrow showed CR in 21 to 28 days after transplantation. All of 7 cases of patients remised in 6 to 47 months after transplantation, and 4 cases died lastly and 3 cases failed to be followed up in A group. The median time of progression-free survival(PFS) was 36(6-47) months, and that of overall survival(OS) was 37(7-50) months. In B group, 2 cases of patients remissed in 5 and 17 months after transplantation, and did lastly, 1 case relieved in 12 months after transplantation and failed to be followed up. 1 case of patient relived in 46 months after transplantation, and then received the second auto-PBHSCT, and got CR for 105 months. Other 10 cases got CR, their median time of PFS was 45.5(4-105) months, the median time of overall survival(OS) was 45.5(4-105) months. The PFS and OS were very significant different between 2 groups (P<0.01). CONCLUSION: Bortezomib-based chemotherapy, Auto-PBHSCT and maintenance treatment with thalidomide were favorable to the patients of MM for survival prolongation.