Synthesis, antibacterial activity, and 3D-QASR studies of matrine-indole derivatives as potential antibiotics.

Matrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). The obtained results demonstrated promising antibacterial efficacy, particularly for compounds A20 and A18, which exhibited MICs.au values of 0.021 and 0.031 mg/ml, respectively, against S. aureus. Moreover, compounds A20 and A27 displayed remarkable MICc.al values of 2.806 and 4.519 mg/ml, respectively, against C. albicans, surpassing the performance of the clinical antibiotic penicillin G sodium (0.0368 mg/ml) and fluconazole (4.849 mg/ml). These findings underscore the significant bacteriostatic activity of the matrine derivatives. Furthermore, to gain a deeper understanding 3D-QSAR modeling was employed, revealing the critical influence of steric structure, charge distribution, hydrophobic interactions, and hydrogen bonding within the molecular structure on the bacteriostatic activity of the compounds. Additionally, molecular docking simulations shed light on the interaction between compound A20 and bacterial proteins, highlighting the involvement of hydrogen bonding, hydrophobic interactions, and π-π conjugation in the formation of stable complexes that inhibit the normal functioning of the proteins. This comprehensive analysis provided valuable insights into the antibacterial mechanism of the novel matrine derivatives, offering theoretical support for their potential application as antibiotics.

Dynamic changes of serum miR-105-3p expression and prognostic value evaluation of postoperative thyroid cancer.

Thyroid cancer (TC) originates from thyroid epithelial cells and is one of the common malignant tumors in the endocrine system. The aim of our study was to explore the dynamic changes of serum miR-105-3p expression after TC surgery and its correlation with clinicopathological manifestations, and evaluate its clinical value as a potential biomarker after surgery. A total of 100 TC patients were selected as the research objects. To detect serum miR-105-3p in patients and its correlation with tumor pathological characteristics and the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker. Serum miR-105-3p increases in patients with well-differentiated TC and lymph node metastasis; Serum miR-105-3p gradually decreases after surgery, and there is a significant difference between 4 days after surgery and before surgery,  serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of TC after surgery. The level of serum miR-105-3p is closely related to tumor differentiation and lymph node metastasis in TC patients. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of TC after surgery and is expected to become a TC surgery. Potential biomarkers for post-diagnosis.

Treated wastewater and weak removal mechanisms enhance nitrate pollution in metropolitan rivers.

The focus of urban water environment renovation has shifted to high nitrate (NO3-) load. Nitrate input and nitrogen conversion are responsible for the continuous increase in nitrate levels in urban rivers. This study utilized nitrate stable isotopes (δ15N-NO3- and δ18O-NO3-) to investigate NO3- sources and transformation processes in Suzhou Creek, located in Shanghai. The results demonstrated that NO3- was the most common form of dissolved inorganic nitrogen (DIN), accounting for 66 ± 14% of total DIN with a mean value of 1.86 ± 0.85 mg L-1. The δ15N-NO3- and δ18O-NO3- values ranged from 5.72 to 12.42‰ (mean value: 8.38 ± 1.54‰) and -5.01 to 10.39‰ (mean value: 0.58 ± 1.76‰), respectively. Based on isotopic evidence, the river received a significant amount of nitrate through direct exogenous input and sewage ammonium nitrification, while nitrate removal (denitrification) was insignificant, resulting in nitrate accumulation. Analysis using the MixSIAR model revealed that treated wastewater (68.3 ± 9.7%), soil nitrogen (15.7 ± 4.8%) and nitrogen fertilizer (15.5 ± 4.9%) were the main sources of NO3- in rivers. Despite the fact that Shanghai's urban domestic sewage recovery rate has reached 92%, reducing nitrate concentrations in treated wastewater is crucial for addressing nitrogen pollution in urban rivers. Additional efforts are needed to upgrade urban sewage treatment during low flow periods and/or in the main stream, and to control non-point sources of nitrate, such as soil nitrogen and nitrogen fertilizer, during high flow periods and/or tributaries. This research provides insights into NO3- sources and transformations, and serves as a scientific basis for controlling NO3- in urban rivers.

Nitrifier adaptation to low energy flux controls inventory of reduced nitrogen in the dark ocean.

Ammonia oxidation to nitrite and its subsequent oxidation to nitrate provides energy to the two populations of nitrifying chemoautotrophs in the energy-starved dark ocean, driving a coupling between reduced inorganic nitrogen (N) pools and production of new organic carbon (C) in the dark ocean. However, the relationship between the flux of new C production and the fluxes of N of the two steps of oxidation remains unclear. Here, we show that, despite orders-of-magnitude difference in cell abundances between ammonia oxidizers and nitrite oxidizers, the two populations sustain similar bulk N-oxidation rates throughout the deep waters with similarly high affinities for ammonia and nitrite under increasing substrate limitation, thus maintaining overall homeostasis in the oceanic nitrification pathway. Our observations confirm the theoretical predictions of a redox-informed ecosystem model. Using balances from this model, we suggest that consistently low ammonia and nitrite concentrations are maintained when the two populations have similarly high substrate affinities and their loss rates are proportional to their maximum growth rates. The stoichiometric relations between the fluxes of C and N indicate a threefold to fourfold higher C-fixation efficiency per mole of N oxidized by ammonia oxidizers compared to nitrite oxidizers due to nearly identical apparent energetic requirements for C fixation of the two populations. We estimate that the rate of chemoautotrophic C fixation amounts to ∼1 × 1013 to ∼2 × 1013 mol of C per year globally through the flux of ∼1 × 1014 to ∼2 × 1014 mol of N per year of the two steps of oxidation throughout the dark ocean.

Forward Collision Warning Strategy Based on Millimeter-Wave Radar and Visual Fusion.

Forward collision warning (FCW) is a critical technology to improve road safety and reduce traffic accidents. However, the existing multi-sensor fusion methods for FCW suffer from a high false alarm rate and missed alarm rate in complex weather and road environments. For these issues, this paper proposes a decision-level fusion collision warning strategy. The vision algorithm and radar tracking algorithm are improved in order to reduce the false alarm rate and omission rate of forward collision warning. Firstly, this paper proposes an information entropy-based memory index for an adaptive Kalman filter for radar target tracking that can adaptively adjust the noise model in a variety of complex environments. Then, for visual detection, the YOLOv5s model is enhanced in conjunction with the SKBAM (Selective Kernel and Bottleneck Attention Mechanism) designed in this paper to improve the accuracy of vehicle target detection. Finally, a decision-level fusion warning fusion strategy for millimeter-wave radar and vision fusion is proposed. The strategy effectively fuses the detection results of radar and vision and employs a minimum safe distance model to determine the potential danger ahead. Experiments are conducted under various weather and road conditions, and the experimental results show that the proposed algorithm reduces the false alarm rate by 11.619% and the missed alarm rate by 15.672% compared with the traditional algorithm.

The effect of near-surface electron trapping layer on the acetone sensing performance of black TiO2capped with ZnO.

In recent years, high-performance acetone gas sensors have attracted great attention for their potential in noninvasive blood glucose monitoring. In this work, black TiO2(B-TiO2) was introduced as an electron trapping layer between TiO2and ZnO to form TiO2@B-TiO2@ZnO core-shell nanoparticles, through a simple and safe method. The acetone sensing performance of TiO2@B-TiO2@ZnO varied with the thickness of ZnO. Because of the electron trapping effect of the introduced B-TiO2layer, the best performing sample exhibited a low optimal operating temperature of 275 °C and a high response of 49.25-50 ppm acetone. In addition, a low detection limit of 170 ppb was obtained. The pretty selectivity of the sample was also been proved. The mechanism of enhanced acetone response was explained by the energy band-based model of TiO2@B-TiO2@ZnO core-shell nanoparticle and depletion layer theory.

Antibiofilm mechanism of a novel milk-derived antimicrobial peptide against Staphylococcus aureus by downregulating agr quorum sensing system.

AIMS: Staphylococcus aureus has emerged as a serious threat to food safety owing to biofilm formation. The study aimed to examine the antibiofilm mechanism of a novel milk-derived antimicrobial peptide BCp12 against it. METHODS AND RESULTS: Antibiofilm activity of BCp12 was studied by crystal violet staining, MTT assay, motility, SEM and CLSM. TMT proteome, real-time PCR and molecular docking in silico were conducted to evaluate the mechanism of BCp12 against S. aureus biofilm. The results showed that BCp12 had significant antibiofilm activity at 1 × MIC and sub-MIC. BCp12 induced the dispersion of structure of S. aureus biofilm BCp12 inhibited the movement of S. aureus. A total of 703 proteins were downregulated and 334 proteins were upregulated after BCp12 treatment. The proteins (agrA, agrB, agrC and psmß) of the QS systems were downregulated. Additionally, the expression of the agr-related genes, agrA, agrB, agrC and psmß, was downregulated. BCp12 was bound to the receptor proteins agrA and agrC through hydrogen bonds and π-π bonds. CONCLUSIONS: The results showed the antibiofilm activity of BCp12 and it inhibits the biofilm formation by interfering agr QS system. SIGNIFICANCE AND IMPACT OF STUDY: BCp12 has the potential to be a novel antibiofilm agent against S. aureus biofilm and used in the food industry.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

High-performance MoOx/n-Si heterojunction NIR photodetector with aluminum oxide as a tunneling passivation interlayer.

The most effective and potential approach to improve the performance of heterojunction photodetectors is to obtain favorable interfacial passivation by adding an insertion layer. In this paper, MoOx/Al2O3/n-Si heterojunction photodetectors with excellent photocurrents, responsivity and detectivity were fabricated, in which alumina acts as a tunneling passivation layer. By optimizing the post-annealing treatment temperature of the MoOxand the thickness of the ultra-thin Al2O3, the photodetector achieved a ratio of photocurrent to dark current of 3.1 × 105, a photoresponsivity of 7.11 A W-1(@980 nm) and a detective of 9.85 × 1012Jones at -5 V bias. Besides, a self-driven response of 0.17 A W-1and a high photocurrent/dark current ratio of 2.07 × 104were obtained. The result demonstrated that optimizing the interface of heterojunctions is a promising way to obtain a heterojunction photodetector with high-performance.

Enzymatic Cleaning Mitigates Polysaccharide-Induced Refouling of RO Membrane: Evidence from Foulant Layer Structure and Microbial Dynamics.

Traditional harsh chemical cleaning-in-place (CIP) is corrosive to membranes but has limited inhibition on refouling, a tough problem for long-term operation of reverse osmosis (RO). Mild enzymatic cleaning (at pH 9) is a promising alternative but lacks long-term verification and insightful elucidation. In this study, we investigated the instantaneous efficiency, postcleaning refouling, and biological effect of enzymatic CIP (compounded with lipase, protease, and sodium dodecyl sulfate) on practical RO membranes during a 500 h multicycle operation. The enzymatic CIP had an average cleaning efficiency of 77%, which is comparable to a commercial harsh CIP benchmark (pH > 12). It mitigated refouling by shaping the biofilm into a loose and porous architecture where newly arrived organics conformed standard blocking, whereas harsh chemicals rendered a smooth and dense gel layer with quick refouling in intermediate blocking or cake filtration mode. Such structural disparities were dominated by polysaccharides according to quantitative chemical analyses. Gene sequencing and ecological network analysis further proved that the behavior of polysaccharide-related keystone species (such as Sphingomonas and Xanthomonas) significantly changed after long-term enzymatic treatment. In this regard, the mild selective pressure of enzymatic reagents can directionally regulate microbial dynamics, alter foulant layer structure via bio-organic synchronicity, mitigate refouling, and eventually improve the sustainability of RO operation.

Ecological determinants of effect of a free pit and fissure sealant program in Shanxi, China, 2017-2018.

BACKGROUND: The aim of this study is to explore the spatial heterogeneity of the retention of PFS in children aged 7-9 years in Shanxi Province, North China and investigate the risk factors associated with PFS retention. METHODS: In this study, 937 children aged 7-9 years from Shanxi Province, China were randomly selected, all of whom had at least one first permanent tooth sealed with PFS in 2016. The children were surveyed after 12 months (in 2017) and 24 months (in 2018). The Geo-detector model was used to explore the spatial heterogeneity of the retention rate of PFS and analyze the influence and interactions of the ecological factors on PFS. RESULTS: 3299 teeth from 937 children were analyzed. The PFS full retention rates after 12 months (in 2017) and 24 months (in 2018) were 81.6% and 75.1%, respectively. The incidence of caries of the first molar was 2.1% after 12 months and 5.4% after 24 months. The spatial heterogeneity of the PFS retention rate after 24 months was significant, which was shown as the retention rate of PFS increased from north to south after 24 months. Remarkably, the natural environmental factors exerted greater influence than the socioeconomic and medical resources factors after 12 months, where the interaction of fluorine in water (FW) had the strongest explanatory power of 52% (P < 0.05). The medical resources were important ecological factors after 24 months, and the percentage of medical technicians (PMT) had the strongest explanatory power of 70% (P < 0.05). CONCLUSION: The natural environmental factors and medical resources factors are important ecological factors determining the spatial pattern. The government should strengthen medical and technician construction in North China, comprehensively control fluoride in water, optimize the allocation of medical resources, and promote the balanced development of regional medicine.

Tumor-suppressive miR-145 co-repressed by TCF4-ß-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer.

The frequently dysregulated Wnt/ß-catenin signaling in different malignancies, by activation of its own or orchestration with other co-factors, regulates various oncogenic or tumor-suppressive genes. Among these genes, miRNAs, which are negative posttranscriptional regulators, are also embedded in the Wnt signaling network. Different from the Wnt-induced oncogenic miRNAs, the specific mechanism underlying the Wnt-repressed tumor-suppressive miRNAs is much less understood. In our study, firstly by analyzing a ChIP-seq dataset against TCF4, the core transcription factor for initiation of Wnt signaling in colorectal cancer (CRC) cells, we screened out several tumor-suppressive miRNAs potentially regulated by Wnt signaling. Then through siRNA-mediated knock-down tests and protein and chromatin immunoprecipitations, we found the TCF4-ß-catenin complex can recruit the histone trimethylation complex PRC2 as a co-repressor while binding to the TCF4-binding element (TBE) in the promoter regions of miR-145, miR-132 and miR-212. Thus, upon Wnt signaling activation, the PRC2-mediated trimethylation of histone H3 at lysine 27 increases at these promoter regions, leading to decreased miRNA levels. Furthermore, we found that by targeting TCF4 and SUZ12, the key components of the negative regulation complexes, the tumor-suppressive miR-145 co-repressed by Wnt signaling and histone trimethylation, forms double-negative regulation loops with its negative regulators in CRC cells. And the inverse associations between miR-145 and its targets/negative regulators have also been demonstrated in nude mice and clinical samples. Collectively, we elucidated the detailed molecular mechanism of how dysregulated Wnt/ß-catenin signaling and tumor-suppressive miRNAs reciprocally regulate each other in CRC cells.

Combined Treatment with Valproic Acid and 5-Aza-2'-Deoxycytidine Synergistically Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration.

BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P. MATERIAL AND METHODS The cell proliferation was detected by xCELLigence RTCA DP Instrument, viability by CCK8 assay, cell apoptosis and cell cycle by flow cytometry, and cell migration by wound healing assay, Transwell assay and xCELLigence RTCA DP Instrument. RESULTS We discovered that VPA and 5-Aza could individually induce decreased viability and have an inhibitory effect on the proliferation of 786-O and 769-P cells. This anti-growth effect was more pronounced when the cells were treated with both VPA and 5-Aza. The combination of VPA and 5-Aza also elicited more apoptosis and produced more cell cycle arrest in the G1 phase for both cell lines. On the other hand, treatment of RCC cells with VPA, 5-Aza, or a combination of both resulted in slow wound healing and impaired migration. CONCLUSIONS These findings clearly demonstrated that VPA combined with 5-Aza could significantly increase anti-RCC effects by inhibiting cellular proliferation, inducing apoptosis, promoting cell cycle arrest and prohibiting the migration of human RCC cells.

Cervical dilation balloon combined with intravenous drip of oxytocin for induction of term labor: a multicenter clinical trial.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of a method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin on the induction of term labor, providing the reference for clinical safety. METHODS: A total of 120 pregnant women with a gestation between 37+0 and  41+6 weeks, indications of labor induction, singleton pregnancy with cephalic presentation were enrolled. The patients were divided into the research group receiving cervical dilation balloon combined with intravenous drip of oxytocin and the control group receiving an intravenous drip of oxytocin at a concentration of 0.5% for labor induction (n = 60 for each). The effectiveness and safety of labor induction were evaluated by the rates of successful cervical ripening promotion and labor induction, as well as the vaginal delivery rate, induced labor time, total duration of labor, the total amount of postpartum hemorrhage within 24 h after giving birth, the incidences of postpartum hemorrhage, cervical laceration, puerperal infection and neonatal outcomes. RESULTS: There was no statistical difference in the basal demographic and clinical characteristics, including ages, gestational weeks, delivery times and Bishop scores at admission between two groups. The rate of successful cervical ripening promotion (research vs. control = 90.00% vs. 55.00%), the rate of successful induction (95.00% vs. 40.00%), the vaginal delivery rate (93.33% vs. 63.33%), the induced labor time (15.03 ± 5.40 vs. 30.68 ± 10.82 h), and the total duration of labor (8.12 ± 2.65 vs. 15.01 ± 6.06 h) were significantly different between two groups (all P < 0.05). There was no significant difference in the total amount of postpartum hemorrhage, incidences of postpartum hemorrhage, cervical laceration, puerperal infection as well as the neonatal outcomes, including neonatal weight, neonatal asphyxia and incidence of meconium aspiration syndrome between two groups. CONCLUSIONS: Compared to labor induction of oxytocin, the method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin for the induction of term labor has a higher vaginal delivery rate, shorter total duration of labor, and does not increase the incidences of postpartum hemorrhage and neonatal infection, which is a more effective and safer method for induction of term labor.

Growth mechanism of Ge-doped CZTSSe thin film by sputtering method and solar cells.

Ge-doped CZTSSe thin films were obtained by covering a thin Ge layer on CZTS precursors, followed by a selenization process. The effect of the Ge layer thickness on the morphologies and structural properties of Ge-doped CZTSSe thin films were studied. It was found that Ge doping could promote grain growth to form a compact thin film. The lattice shrank in the top-half of the film due to the smaller atomic radius of Ge, leading to the formation of tensile stress. According to thermodynamic analysis, Sn was easier to be selenized than Ge. Thus, Ge preferred to remain on the surface and increased the surface roughness when the Ge layer was thin. CZTSe was easier to form than Ge-doped CZTSe, which caused difficulty in Ge doping. These results offered a theoretical and experimental guide for preparing Ge-doped CZTSSe thin films for the potential applications in low-cost solar cells. With a 10 nm Ge layer on the top of the precursor, the conversion efficiency of the solar cell improved to 5.38% with an open-circuit voltage of 403 mV, a short-circuit current density of 28.51 mA cm-2 and a fill factor of 46.83% after Ge doping.

[Development of a Laser On-Line Cement Raw Material Analysis Equipment].

In engineering construction, cement quality directly affects the safety of construction projects. So it is necessary that we use qualified cement in the engineering structure. It is of great signification that a method detects cement raw material rapidly to adjust the mixture ratio of raw ores to ensure the cement quality. Traditional detection method needs sampling, sample preparation and test, etc. With many procedures, the test results are seriously lagged behind the production process. This paper introduces a set of online analysis equipment to determinate elemental composition of cement powder timely based on laser induced breakdown spectroscopy. This equipment is composed of a LIBS detection system and a pneumatic system. The equipment can achieve the real-time measurement for it needn't sample preparation. Thus, it can guide cement raw material proportioning in time. In this paper, we have quantitatively analyzed the main components of Al2O3, CaO, Fe2O3, MgO and SiO2 in the cement raw materials using the full spectrum normalization method as well as the support vector machine. The corresponding maximum absolute errors were 0.34%, 0.35%, 0.07%, 0.14%, and 0.55%, respectively. Results showed that the measurement results of the newly developed LIBS equipment are in accord with those of the conventional chemical method. Furthermore, the measurement precision is in line with X-Ray fluorescence spectrometry. It is confirmed that the LIBS technique could be a prospect method for determination of elemental composition in the cement production industries.

[Mechanisms for inhibitory effect of ALDH2 on doxorubicin-induced cytotoxicity in C2C12 myogenic cell line].

OBJECTIVE: To investigate the mechanisms for inhibitory effect of aldehyde dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12 myogenic cell line.
 METHODS: Cell apoptosis was evaluated by flow cytometry and the activity of capase-3/7. The relative content of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2 (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and quantitative PCR, respectively. 
 RESULTS: Overexpression of ALDH2 attenuated DOX-induced cell toxicity (increase in apoptosis and inhibition of proliferation), which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS production, which were reversed by downregulation of ALDH2. Moreover, apocynin, an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity, and an increase in the activity and expression of ALDH2. 
 CONCLUSION: DOX-induced cytotoxicity is related to increase of intracellular oxidative stress, which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.

MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2.

miR-221/222 are two highly homologous microRNAs that are frequently upregulated in solid tumors. However, the effects of miR-221/222 in malignant gliomas have not been investigated thoroughly. In this study, we found that miR-221/222 were significantly upregulated in human glioma samples and glioma cell lines. Both gain- and loss-of-function studies showed that miR-221/222 regulate cell proliferation, the cell cycle and apoptosis, in addition to, invasion, metastasis, and angiogenesis in glioma cell lines. Subsequent investigations revealed that TIMP2 is a direct target of miR-221/222, and overexpression of TIMP2 reduced the miR-221/222-mediated invasion, metastasis, and angiogenesis of glioma cells. Taken together, our results suggest that the suppression of miR-221/222 may be a feasible approach for inhibiting the malignant behaviors of glioma.

Predicting potentially avoidable hospitalizations.

BACKGROUND: Hospitalizations due to ambulatory care sensitive conditions (ACSCs) are widely accepted as an indicator of primary care access and effectiveness. However, broad early intervention to all patients in a health care system may be deemed infeasible due to limited resources. OBJECTIVE: To develop a predictive model to identify high-risk patients for early intervention to reduce ACSC hospitalizations, and to explore the predictive power of different variables. METHODS: The study population included all patients treated for ACSCs in the VA system in fiscal years (FY) 2011 and 2012 (n=2,987,052). With all predictors from FY2011, we developed a statistical model using hierarchical logistic regression with a random intercept to predict the risk of ACSC hospitalizations in the first 90 days and the full year of FY2012. In addition, we configured separate models to assess the predictive power of different variables. We used a random split-sample method to prevent overfitting. RESULTS: For hospitalizations within the first 90 days of FY2012, the full model reached c-statistics of 0.856 (95% CI, 0.853-0.860) and 0.856 (95% CI, 0.852-0.860) for the development and validation samples, respectively. For predictive power of the variables, the model with only a random intercept yielded c-statistics of 0.587 (95% CI, 0.582-0.593) and 0.578 (95% CI, 0.573-0.583), respectively; with patient demographic and socioeconomic variables added, the c-statistics improved to 0.725 (95% CI, 0.720-0.729) and 0.721 (95% CI, 0.717-0.726), respectively; adding prior year utilization and cost raised the c-statistics to 0.826 (95% CI, 0.822-0.830) and 0.826 (95% CI,0.822-0.830), respectively; the full model was reached with HCCs added. For the 1-year hospitalizations, only the full model was fitted, which yielded c-statistics of 0.835 (95% CI, 0.831-0.837) and 0.833 (95% CI, 0.830-0.837), respectively, for development and validation samples. CONCLUSIONS: Our analyses demonstrate that administrative data can be effective in predicting ACSC hospitalizations. With high predictive ability, the model can assist primary care providers to identify high-risk patients for early intervention to reduce ACSC hospitalizations.

Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor: A SEER-Based Study.

OBJECTIVES: Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood. MATERIALS AND METHODS: The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients. RESULTS: The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C -indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively. CONCLUSIONS: The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.