Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis.

BACKGROUND: The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB). METHODS: This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi'an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model. RESULTS: Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes. CONCLUSIONS: We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.

Probing

The isomer depletion of ^{93m}Mo was recently reported [Chiara et al., Nature (London) 554, 216 (2018)NATUAS0028-083610.1038/nature25483] as the first direct observation of nuclear excitation by electron capture (NEEC). However, the measured excitation probability of 1.0(3)% is far beyond the theoretical expectation. In order to understand the inconsistency between theory and experiment, we produce the ^{93m}Mo nuclei using the ^{12}C(^{86}Kr,5n) reaction at a beam energy of 559 MeV and transport the reaction residues to a detection station far away from the target area employing a secondary beam line. The isomer depletion is expected to occur during the slowdown process of the ions in the stopping material. In such a low γ-ray background environment, the signature of isomer depletion is not observed, and an upper limit of 2×10^{-5} is estimated for the excitation probability. This is consistent with the theoretical expectation. Our findings shed doubt on the previously reported NEEC phenomenon and highlight the necessity and feasibility of further experimental investigations for reexamining the isomer depletion under low γ-ray background.

Observation of a Strongly Isospin-Mixed Doublet in

ß decay of proton-rich nuclei plays an important role in exploring isospin mixing. The ß decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through ß-delayed two-proton emission (ß2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P ß decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in ß-decay experiments.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

[A study of the relations of foramen rotundum structure direction and the approach of percutaneous puncturing of radiofrequency thermocoagulation for treating V2 of primary trigeminal neuralgia].

Objective: To investigate the relations of foramen rotundum structure direction and surrounding structure systematically in order to choose the best approach of percutaneous puncturing of radiofrequency thermocoagulation for treating V2 of primary trigeminal neuralgia. Methods: A total of 122 patients with V2 of primary trigeminal neuralgia for radiofrequency thermocoagulation were enrolled from August 2012 to May 2017 at the First Hospital of Jiaxing. CT scan images were observed retrospectively, to find the inside and outside of the foramen rotundum. The direction of foramen rotundum were recorded and the best approach of puncturing were analyzed. Results: The images were divided into four quadrants with the semi - coronal CT scan plane of the lower margin of the zygomatic arch and the outer edge of foramen rotundum for horizontal axis, and the sagittal plane for the vertical axis. In 122 cases, foramen rotundum direction in outer upper quadrant were 77 cases(63.1%), and in outer under quadrant were 22 cases(18.0%), and in inner upper quadrant were 19 cases(15.6%), and in inner under quadrant were 4 cases(3.3%). Conclusion: The most common foramen rotundum direction is in outer upper quadrant, so the best approach of percutaneous puncturing of radiofrequency thermocoagulation for treating V2 of primary trigeminal neuralgia is the upper side against zygomatic and the inner side against the wall of maxillary sinus.

[Dose-response relationship of ropivacaine for epidural block in early herpes zoster guided by CT].

Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval (CI) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant(Z=2.576, P=0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P=0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant (Z=17.421, P=0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95%CI) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for epidural block in early herpes zoster guided by CT is effective for neuropathic pain, with no significant adverse reactions.

Effect of polymorphisms in interleukin-18 gene on the susceptibility to coronary artery disease in a Chinese population.

Coronary artery disease (CAD) has a high mortality rate in several countries. Interleukin (IL)-18 has been previously correlated with atherosclerotic plaque rupture. In this case-control study, the relationship between -607A/C and -372C/G promoter polymorphisms in IL-18 and risk of CAD development was investigated. A total of 326 CAD patients were consecutively recruited from the First Hospital of Yulin between March 2013 and May 2015. The IL-18 -607A/C and -372C/G polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Patients with CAD had a higher body mass index, a history of hypertension or diabetes (all P < 0.001), cigarette smoking habit (P = 0.002); as well as higher plasma total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels (all P < 0.001) and lower high-density lipoprotein cholesterol (P < 0.001) levels compared to the control subjects. Unconditional logistic regression analysis revealed significant correlation between the CC genotype of IL-18 -607A/C and CAD development, compared to the AA genotype [adjusted odds ratio (OR) = 2.42; 95% confidence interval (CI) = 1.52-3.89; P < 0.001]. The recessive model showed a significant association between the CC genotype of IL-18 -607A/C and an increased risk of CAD, compared to the AA+AC genotype (OR = 2.51, 95%CI = 1.65-3.85). However, IL-18 -372C/G did not contribute to the risk of glioma development in the co-dominant, dominant, and recessive models. Therefore, the IL-18 -607C/A polymorphism was significantly correlated with the risk of CAD development.

Observation of enhanced monopole strength and clustering in (12)Be.

In a recent breakup-reaction experiment using a Be12 beam at 29 MeV/nucleon, the 0+ band head of the expected He4+He8 molecular rotation was clearly identified at about 10.3 MeV, from which a large monopole matrix element of 7.0±1.0 fm2 and a large cluster-decay width were determined for the first time. These findings support the picture of strong clustering in Be12, which has been a subject of intense investigations over the past decade. The results were obtained thanks to a specially arranged detection system around zero degrees, which is essential in determining the newly emphasized monopole strengths to signal the cluster formation in a nucleus.

The gendered behaviors displayed by Disney protagonists.

Previous research suggests that the portrayal of male and female protagonists in Disney animations may be changing over time. The current study examined the portrayal of gendered behaviors displayed within some of Disney's most successful animated feature length films, including those beyond the Disney princess franchise. Extending the scope of the Disney animated films analyzed was important because both young girls and young boys report little personal interest in male characters within the Disney princess animations. This suggests that it is important to look beyond the Disney princess franchise to understand the gendered behaviors displayed by potentially influential male Disney protagonists. The current study also considered a greater number of masculine and feminine behaviors as well as some gender-neutral traits which had yet to be incorporated. A quantitative content analysis of 39 Disney protagonists from films released between 1937 and 2021 was conducted. The results revealed that male and female protagonists were statistically higher in feminine than masculine traits. Female protagonists from the earliest animations were the most feminine. However, there was no statistical difference in the gendered portrayals of females in the animations released in the 1990s and those released from 2009 to 2021 suggesting some continued stereotyping in females' profiles. Alternatively, male characters were more feminine relatively consistently across time-points. This study concludes that Disney is persistently portraying stereotyped female protagonists, and this could have implications on young females' behavioral profiles. However, the extent to which feminine traits are being celebrated when displayed by male protagonists needs to be examined, as well as the potential relationship between such messages and boys' behaviors and children's conceptualizations of gender more broadly.

MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1.

This paper presents several inaccuracies and mistakes. Therefore, the article "MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1, by R.-K. Zang, J.-B. Ma, Y.-C. Liang, Y. Wang, S.-L. Hu, Y. Zhang, W. Dong, W. Zhang, L.-K. Hu, published in Eur Rev Med Pharmacol Sci 2018; 22 (14): 4532-4541-DOI: 10.26355/eurrev_201807_15508-PMID: 30058693" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15508.

Comparison of the clinical and CT features between COVID-19 and H1N1 influenza pneumonia patients in Zhejiang, China.

OBJECTIVE: To explore the different clinical and CT features distinguishing COVID-19 from H1N1 influenza pneumonia. PATIENTS AND METHODS: We compared two independent cohorts of COVID-19 pneumonia (n=405) and H1N1 influenza pneumonia (n=78), retrospectively. All patients were confirmed by RT-PCR. Four hundred and five cases of COVID-19 pneumonia were confirmed in nine hospitals of Zhejiang province, China from January 21 to February 20, 2020. Seventy-eight cases of H1N1 influenza pneumonia were confirmed in our hospital from January 1, 2017 to February 29, 2020. Their clinical manifestations, laboratory test results, and CT imaging characteristics were compared. RESULTS: COVID-19 pneumonia patients showed less proportions of underlying diseases, fever and respiratory symptoms than those of H1N1 pneumonia patients (p<0.01). White blood cell count, neutrophilic granulocyte percentage, C-reactive protein, procalcitonin, D-Dimer, and lactate dehydrogenase in H1N1 pneumonia patients were higher than those of COVID-19 pneumonia patients (p<0.05). H1N1 pneumonia was often symmetrically located in the dorsal part of inferior lung lobes, while COVID-19 pneumonia was unusually showed as a peripheral but non-specific lobe distribution. Ground glass opacity was more common in COVID-19 pneumonia and consolidation lesions were more common in H1N1 pneumonia (p<0.01). COVID-19 pneumonia lesions showed a relatively clear margin compared with H1N1 pneumonia. Crazy-paving pattern, thickening vessels, reversed halo sign and early fibrotic lesions were more common in COVID-19 pneumonia than H1N1 pneumonia (p<0.05). Pleural effusion in COVID-19 pneumonia was significantly less common than H1N1 pneumonia (p<0.01). CONCLUSIONS: Compared with H1N1 pneumonia in Zhejiang, China, the clinical manifestations of COVID-19 pneumonia were more concealed with less underlying diseases and slighter respiratory symptoms. The more common CT manifestations of COVID-19 pneumonia included ground-glass opacity with a relatively clear margin, crazy-paving pattern, thickening vessels, reversed halo sign, and early fibrotic lesions, while the less common CT manifestations of COVID-19 pneumonia included consolidation and pleural effusion.

LncRNA H19 inhibitor represses synovial cell proliferation and apoptosis in rats with rheumatoid arthritis via Notch signaling pathway.

The article "LncRNA H19 inhibitor represses synovial cell proliferation and apoptosis in rats with rheumatoid arthritis via Notch signaling pathway, by L.-Q. Zhi, Q. Zhong, J.-B. Ma, L. Xiao, S.-X. Yao, X. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (8): 4088-4094-DOI: 10.26355/eurrev_202004_20985-PMID: 32373945" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20985.

LncRNA H19 inhibitor represses synovial cell proliferation and apoptosis in rats with rheumatoid arthritis via Notch signaling pathway.

OBJECTIVE: To study the roles and underlying mechanisms of long non-coding ribonucleic acid (lncRNA) H19 in the synovial cell proliferation and apoptosis in rats with rheumatoid arthritis (RA). MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were randomly divided into Control group and Model group. The rat model of RA was induced by using type II collagen in Model group. The primary synovial cells were isolated from the synovial tissues of the rats and were assigned into Control group, Model group, and lncRNA H19 inhibitor intervention group. 5-Ethynyl-2'-deoxyuridine (EdU) staining was applied to detect cell proliferation in each group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was employed to determine the cell apoptosis in each group. Western blotting assay was adopted to measure the expression levels of Notch1 and hairy/enhancer of split-1 (Hes1) in each group of cells. RESULTS: The RA score of the Model group was higher than that of the Control group. Compared to the Control group, the expression of lncRNA H19, Notch, and Hes1 of the synovial cells in the Model group were significantly elevated. Besides, the cell proliferation rate of the Model was also increased, while the cell apoptosis rate was decreased compared with those in the Control group. Moreover, in comparison with Model group, lncRNA H19 inhibitor intervention group exhibited a lowered lncRNA H19 level, remarkably reduced cell proliferation rate and protein levels of Notch1 and Hes1, as well as notably raised cell apoptosis rate. CONCLUSIONS: Our results indicated that lncRNA H19 inhibitor could repress the proliferation and promote the apoptosis of synovial cells in RA rats, which might be attributed to the inhibition of the Notch signaling pathway.

Circ-ABCB10 promotes proliferation and invasion of esophageal squamous cell carcinoma cells by modulating microRNA-670-3p.

OBJECTIVE: Circ-ABCB10 is a non-coding RNA newly discovered in recent years. It has been observed to serve as an oncogene in a variety of tumors, but its biological function in esophageal squamous cell carcinoma (ESCC) is still unknown. The purpose of this study was to investigate the circ-ABCB10 expression in ESCC and its possible molecular mechanism. PATIENTS AND METHODS: Circ-ABCB10 expression in ESCC tissue samples and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of circ-ABCB10 on the biological functions of ESCC cells were examined by cell counting kit-8 (CCK-8) and transwell assays. Moreover, bioinformatics analysis was used to determine the binding sites between miRNAs and circ-ABCB10, and the binding relationship was verified by qRT-PCR and Luciferase assay. RESULTS: QRT-PCR analysis revealed that circ-ABCB10 expression in both ESCC tissues and cell lines was higher than that in the normal control group. Patients in high TNM stage exhibited a higher expression of circ-ABCB10 than those in low stage, and this high expression predicted a poor prognosis of ESCC patients. Inhibiting circ-ABCB10 expression remarkably inhibited the growth and metastasis of ESCC cells. In addition, it was demonstrated that circ-ABCB10 could bind to microRNA-670-3p and inhibit its expression. Downregulation of microRNA-670-3p partially reversed the inhibitory impact of low-expressing circ-ABCB10 on cell growth and migration rate. CONCLUSIONS: Circ-ABCB10 accelerates the metastasis and proliferation of ESCC cells by binding to microRNA-670-3p. This circ-ABCB10 / microRNA-670-3p axis may become a potential therapeutic target for ESCC therapy.

LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells.

OBJECTIVE: The aim of this study was to elucidate the biological function of long non-coding RNA (lncRNA) HOTTIP (HOXA transcript at the distal tip) in the development of acute myeloid leukemia (AML), and to investigate the potential mechanism. PATIENTS AND METHODS: Relative expression levels of HOTTIP, microRNA-608 and DDA1 in AML patients were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). Meanwhile, the expressions of these genes in AML cell lines were detected as well. The regulatory effects of HOTTIP, microRNA-608 and DDA1 on the proliferative ability and cell cycle progression of AML cells were examined by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Dual-luciferase reporter gene assay was performed to confirm the binding condition of microRNA-608 to HOTTIP and DDA1. Finally, the specific role of HOTTIP/microRNA-608/DDA1 axis in the development of AML was verified through a series of rescue experiments. RESULTS: HOTTIP was highly expressed in AML-M5 patients than normal controls. No significant difference in HOTTIP expression was found between patients with other subtypes of AML (M0, M1, M2, M3, M4 and M6) and normal controls. HOTTIP expression was significantly up-regulated in AML cell lines U-937 and THP-1. Up-regulation of HOTTIP remarkably promoted the proliferative potential and cell cycle progression of AML cells. Dual-luciferase reporter gene indicated that HOTTIP could bind to microRNA-608, which was lowly expressed in AML-M5 patients. Overexpression of microRNA-608 significantly inhibited the proliferative ability and cell cycle progression of U-937 and THP-1 cells. More importantly, microRNA-608 could partially reverse the regulatory effect of HOTTIP on AML cells. Meanwhile, DDA1 was verified as the target of microRNA-608. Subsequent experiments elucidated that DDA1 significantly accelerated the proliferation and cell cycle of AML cells. Furthermore, DDA1 could reverse the inhibitory effect of microRNA-608 on proliferative ability and cell cycle progression of AML cells. CONCLUSIONS: HOTTIP accelerated the proliferative ability and cell cycle of AML cells via up-regulating DDA1 expression by sponging microRNA-608.

MicroRNA-487a promotes proliferation of esophageal cancer cells by inhibiting p62 expression.

OBJECTIVE: MicroRNAs are endogenous, non-coding, small RNAs that can regulate biological processes. Previous studies have found that microRNA-487a serves as an oncogene. However, the role of microRNA-487a in esophageal cancer (EC) has not been reported. The aim of this investigation was to investigate the biological role of microRNA-487a in EC and its underlying mechanism. PATIENTS AND METHODS: The expression of microRNA-487a in 65 pairs of EC tissues and para-cancerous tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-487a expression with age, sex, clinical stage and distant metastasis of OS patients. Kaplan-Meier survival analysis was conducted to evaluate the correlation between microRNA-487a expression and prognosis of EC patients. Subsequently, microRNA-487a expression in EC cell lines was detected as well. After microRNA-487a knockdown, cell counting kit-8 (CCK-8), EdU and transwell assay were conducted to evaluate the role of microRNA-487a in the biological performances of EC cells, respectively. Meanwhile, the apoptosis of EC cells was determined using flow cytometry. Finally, the interaction between microRNA-487a and p62 was explored by Western blot. Transwell assay was carried out in EC cells co-transfected with p62 overexpression plasmid and si-microRNA-487a. RESULTS: Compared with para-cancerous tissues, microRNA-487a expression was significantly higher in EC tissues, and the difference was statistically significant. MicroRNA-487a was highly expressed in EC cells as well. Low expression of microRNA-487a was positively correlated with clinical stage, whereas was not correlated with age, sex, lymph node metastasis and distant metastasis of EC patients. Kaplan-Meier survival curves showed that high expression of microRNA-487a was markedly associated with poor prognosis of EC. The knockdown of microRNA-487a significantly inhibited proliferative, migratory and invasive abilities of EC cells but induced cell apoptosis. Western blot results showed that the protein expression of p62 was remarkably upregulated after microRNA-478a knockdown in EC cells. Transwell assay demonstrated that co-transfection with overexpression plasmid of p62 and si-microRNA-487a in EC cells markedly decreased invasive and migratory abilities. CONCLUSIONS: MicroRNA-487a is highly expressed in EC and is closely correlated with clinical stage and poor prognosis of EC. Our findings confirm that microRNA-487a promotes malignant progression of EC by regulating p62 expression.

MicroRNA-124 inhibits proliferation and metastasis of esophageal cancer via negatively regulating NRP1.

OBJECTIVE: MicroRNAs are a kind of endogenous, non-coding RNAs, which exert a significant role in pathological processes. Previous studies have reported that microRNA-124 is a tumor suppressor. The specific effect of microRNA-124 on esophageal cancer, however, has not been fully elucidated. This study aims to explore the role of microRNA-124 in esophageal cancer and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-124 expressions in 75 esophageal cancer tissues, paracancerous tissues, and esophageal cancer cell lines were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). The relationship between microRNA-124 expression, clinical progression, pathological indicators, and prognosis of patients with esophageal cancer was analyzed. For in vitro experiments, we performed CCK-8 (cell counting kit-8), colony formation and transwell assay to detect cell proliferation, migration, and invasion abilities after microRNA-124 overexpression in TE-1 and EC-109 cells, respectively. Western blot was utilized to explore the regulatory role of microRNA-124 in esophageal cancer cells. RESULTS: MicroRNA-124 was downregulated in esophageal cancer tissues than that of paracancerous tissues. Patients with esophageal cancer who had lower expression level of microRNA-124 presented higher tumor stage and metastasis incidence, as well as lower survival rate. In vitro studies demonstrated a decreased cell proliferation and migration abilities after microRNA-124 overexpression. Western blot results showed upregulated PI3K and AKT, and downregulated PTEN in esophageal cancer cells after overexpression of microRNA-124. Furthermore, microRNA-124 was confirmed to negatively regulate NRP1, so as to participate in the development of esophageal cancer. CONCLUSIONS: MicroRNA-124 is downregulated in esophageal cancer tissues, which is remarkably correlated to the development, pathological grade, and poor prognosis of esophageal cancer. Overexpressed microRNA-124 is capable of inhibiting the malignant progression of esophageal cancer via negatively regulating NRP1.

The expression and mechanism of BDNF and NGB in perihematomal tissue in rats with intracerebral hemorrhage.

OBJECTIVE: To analyze how changes in the levels of brain-derived neurotrophic factor (BDNF) and neuroglobin (NGB) affect learning and memory in rats with intracerebral hemorrhage. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into the control group, sham operation group and model group with 10 rats each. The rats in the control group were untreated, while those in the sham operation group were treated with sterile saline instead of type VII collagenase injection in the globus pallidus. The model of cerebral hemorrhage was established according to the methods described by Rosenberg. The expression of perihematomal BDNF mRNA was measured by Real-time quantitative PCR (RT-PCR) for 7 days consecutively. Perihematomal NGB-positive cells were detected by immunohistochemistry. The Morris water maze was used to test the spatial learning and memory of rats. RESULTS: Compared with the control group and sham operation group, the expression of BDNF mRNA and number of NGB-positive cells in the model group were significantly higher. Furthermore, the escape latency was significantly prolonged (p < 0.05). The NGB and BDNF mRNA levels and escape latency were positively correlated. The correlation coefficients were as follows: rs (NGB) = 1.1838 (p = 0.008); rs (BDNF) = 0.5948 (p = 0.012). CONCLUSIONS: Cerebral hemorrhage significantly inhibited the spatial learning and memory ability of rats. The mechanism may be related to decreased cerebral expression of BDNF and NGB.

Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption.

To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100-230nm were prepared by the salting out method with NaCl and encapsulated via the layer-by-layer (LbL) adsorption to provide the insulin nanoparticles shelled with two oppositely charged polyelectrolytes. Poly(alpha,beta-l-malic acid) (PMA) and water-soluble chitosan (WSC) as the weak polyelectrolytes with good biodegradability and biocompatibility in vivo were chosen to be the encapsulating materials of the LbL adsorption. In the preparation of the insulin nano-aggregates, the NaCl concentration and pH in the medium obviously affected yield and particle size of the insulin nano-aggregates. After eight adsorption cycles of the polyelectrolytes on the insulin nano-aggregates, the insulin-polyelectrolyte nanoparticles with the sizes of 100-250nm were obtained with about 20% insulin loss. The insulin release from the nanoparticles was mostly pH-dependent owing to sensitivity of the weak polyelectrolytes to pH. Insulin was hardly released from the nanoparticles in a medium at pH 4-5 while it could be released at pH 7.4, corresponding to the pH of the human blood and the body fluid. A burst effect was also observed although it could be reduced via increasing the polyelectrolyte layers of PMA and WSC assembled on insulin nano-aggregates.