Effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety in patients with triple-negative breast cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to systematically assess the effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety of patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This study searched for case-control trials of TNBC patients from January 2010 to May 2022. Two researchers independently extracted data. RevMan 5.3 statistical software was used for analysis. RESULTS: This study included a total of 7 clinical controlled studies, containing 620 samples. The results showed that compared with the control group, the study group showed significant differences in objective response rate [OR = 2.44, 95% CI (1.69, 3.5), p < 0.00001], 1-year survival rate [OR = 3.59, 95% CI (2.01, 6.39), p < 0.0001], progression-free survival (PFS) [MD = 2.04, 95% CI (1.68, 2.41), p < 0.00001], with statistical significance (p < 0.05), while there are no significant differences in overall survival [MD = 6.33, 95% CI (-1.65, 14.30), p = 0.12] and incidence of adverse events [OR = 0.73, 95% CI (0.52, 1.02), p = 0.006] (p > 0.05). CONCLUSIONS: Targeted therapy associated with adjuvant chemotherapy can remarkably enhance the outcome of patients with advanced TNBC, prolonging their progression-free survival (PFS) and overall survival (OS) without increasing adverse effects. The validity of this research, however, will require higher quality studies and longer follow-ups.

Modeling functional network topology following stroke through graph theory: functional reorganization and motor recovery prediction

The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain's functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain's FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.

DUXAP8 promotes the proliferation and migration of ovarian cancer cells via down-regulating microRNA-29a-3p expression.

OBJECTIVE: To study the role of long-chain non-coding RNA (lncRNA) DUXAP8 in ovarian cancer (OCa) and the underlying potential mechanism. PATIENTS AND METHODS: The expression pattern of DUXAP8 in ovarian cancer was analyzed using the GEPIA database. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DUXAP8 in OCa tissues; at the same time, OCa cell lines were cultured to complete functional experiments, including cell counting kit-8 (CCK-8), plate cloning experiments and transwell experiments to evaluate the effects of DUXAP8 on the proliferative and migration ability of OCa cell lines. Bioinformatics analysis and Dual-Luciferase reporter genes were used to determine the binding and expression of DUXAP8 to its downstream key gene microRNA-29a-3p in OCa cells. In addition, co-transfection technology and cell function recovery experiments were used to verify the important role of the DUXAP8/microRNA-29a-3p regulatory network in OCa. RESULTS: DUXAP8 was abnormally highly up-regulated in OCa tissues and cell lines, besides, its expression was related to poor prognosis of patients. CCK-8 and plate cloning experiments showed that knockdown of DUXAP8 in OCa cells can significantly inhibit the proliferation of OCa cells. Transwell results suggested that knockdown of DUXAP8 can significantly inhibit OCa cell migration. In addition, it was found that DUXAP8 can bind and negatively regulate the expression of microRNA-29a-3p in OCa. Functional experiments in OCa cells also revealed that microRNA-29a-3p was a key downstream gene that mediated the regulation of DUXAP8 on OCa function. CONCLUSIONS: DUXAP8 has abnormally high expression in OCa and can lead to malignant progression of the tumor.

Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Electrical stimulation at the dorsal root ganglion preserves trabecular bone mass and microarchitecture of the tibia in hindlimb-unloaded rats.

SUMMARY: This study seeks to investigate the effect of electrical stimulation (ES) at dorsal root ganglion (DRG) on disuse bone loss in a rat model. Hindlimb unloading for 14 days resulted in significant bone loss in rat tibia while rats with ES at DRG showed a significant reduced bone loss INTRODUCTION: Mechanical unloading induces osteoporosis in both human and animals. Previous studies demonstrated that electrical stimulation (ES) to dorsal root ganglion (DRG) could trigger secretion of calcitonin gene-related peptide (CGRP) which plays an important role in bone modeling and remodeling. This study seeks to investigate the effect of ES to DRG on disuse bone loss in a rat model. METHODS: Twenty-four rats were randomly assigned in three experimental groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with ES (HUES). ES was applied via implantable micro-electrical stimulators (IMES) to right DRGs at vertebral levels L4-L6 in HUES group. RESULTS: Hindlimb unloading for 14 days resulted in 25.9% decrease in total bone mineral content (BMC), 29.2% decrease in trabecular BMD and trabecular microarchitecture and connectivity were significantly deteriorated in the proximal tibia metaphysis in HU group, while rats with ES at DRG showed significant reduced bone loss that there was 3.8% increase in total BMC, 2.3% decrease in trabecular BMD, and significant improvement in trabecular microarchitecture. There was a concurrent enhancement of expression of CGRP in stimulated DRGs. CONCLUSIONS: The results confirm the effect of ES at DRG on enhancing CGRP expression and suggest potential applications of IMES for the prevention and treatment of disuse bone loss.

Effect of You Gui Wan on mouse sperm fertilising ability in vivo and in vitro.

This study is to explore whether YGW has an impact on sperm fertilising ability in mice. Twenty male mice were randomly divided into two groups. In vivo experiments, one group of animals were orally administrated with YGW decoction and another group administered with saline for 14 days. Afterwards, the animals were mated with their female partners. Percentages of retrieved zygotes were then compared. In vitro experiments, in vitro fertilisation (IVF) assay, sperm acrosome reaction and acrosin activity were used to compare sperm fertilising ability between the two groups. The YGW-treated group had a significantly higher percentage of zygotes than the saline controls (P = 0.005). The IVF rates induced by spermatozoa from the herb-treated mice were also significantly higher than those from the control animals (P = 0.015). The sperm acrosin activity of the herb-treated group was significantly higher than that of the saline-treated group (P = 0.048), although there was no significant difference in testicular weight, sperm count and sperm motility. These data suggest that YGW decoction has a significant effect on normal sperm fertilising ability both in vivo and in vitro, which may be due to, at least in part, increments in the sperm acrosin activity.

Diagnosis and treatment of 29 cases of adrenal ganglioneuroma.

AIM: To evaluate diagnosis and treatment experience for adrenal ganglioneuroma and provide data for clinical surgery. PATIENTS AND METHODS: Analysis clinical feature and iconography and endocrine examination and clinical data of 29-cases adrenal ganglioneuroma in our Hospital. RESULTS: Back discomfort in 10 cases and convulsivum dizziness in 6-cases (hypertension in 2 cases), central obesity in 1 case. 12-cases were found by physical examination. 9-cases were diagnosed as adrenal ganglioneuroma and others were diagnosed as adrenal tumor. After operation, all of the cases were diagnosed as adrenal ganglioneuroma by pathology. Beside one patient were still dizzy with BP (blood pressure): 150/95 mmHg, all of patients completly recovered. CONCLUSIONS: For diagnosis on adrenal ganglioneuroma, we should depend on iconography and pathology. The operation is main method and most of patients can be cured.

BD750, a benzothiazole derivative, inhibits T cell proliferation by affecting the JAK3/STAT5 signalling pathway.

BACKGROUND AND PURPOSE: A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action. EXPERIMENTAL APPROACH: T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK-8 assay. Cytokine levels were measured by elisa. The activation of signal-regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed-type hypersensitivity. KEY RESULTS: BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti-CD3/anti-CD28 monoclonal antibodies or by an alloantigen, in a dose-dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL-2 and IL-4 secretion, but induced cell cycle arrest at the G(0) /G(1) phase in activated T cells. In IL-2-stimulated CTLL-2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell-mediated delayed-type hypersensitivity response in mice in a dose-dependent manner. CONCLUSION AND IMPLICATIONS: These data indicate that BD750 inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases.

NAA and NAAG variation in neuronal activation during visual stimulation

N-acetyl-aspartyl-glutamate (NAAG) and its hydrolysis product N-acetyl-L-aspartate (NAA) are among the most important brain metabolites. NAA is a marker of neuron integrity and viability, while NAAG modulates glutamate release and may have a role in neuroprotection and synaptic plasticity. Investigating on a quantitative basis the role of these metabolites in brain metabolism in vivo by magnetic resonance spectroscopy (MRS) is a major challenge since the main signals of NAA and NAAG largely overlap. This is a preliminary study in which we evaluated NAA and NAAG changes during a visual stimulation experiment using functional MRS. The paradigm used consisted of a rest period (5 min and 20 s), followed by a stimulation period (10 min and 40 s) and another rest period (10 min and 40 s). MRS from 17 healthy subjects were acquired at 3T with TR/TE = 2000/288 ms. Spectra were averaged over subjects and quantified with LCModel. The main outcomes were that NAA concentration decreased by about 20% with the stimulus, while the concentration of NAAG concomitantly increased by about 200%. Such variations fall into models for the energy metabolism underlying neuronal activation that point to NAAG as being responsible for the hyperemic vascular response that causes the BOLD signal. They also agree with the fact that NAAG and NAA are present in the brain at a ratio of about 1:10, and with the fact that the only known metabolic pathway for NAAG synthesis is from NAA and glutamate.

Incidence and survival of symptomatic lacunar infarction in a Beijing population: a 6-year prospective study.

BACKGROUND AND PURPOSE: The incidence of ischaemic stroke has increased or remained high in China; however, little population-based evidence is available on the incidence and survival of lacunar infarction (LAC). We examined the incidence of LAC in a northern Chinese (Beijing) population and monitored survival. METHODS: A prospective registry population-based study was conducted over a 6-year period in a general, unselected, and representative community in Beijing with approximately 100,000 long-term permanent residents. All first-ever stroke cases were registered. RESULTS: A total of 1184 patients with ischaemic stroke were identified; 36.9% (437 cases) were classified as LAC. Age-standardized incidence rates of LAC ranged from 24.0 to 51.3/100,000 with an average rate of 35.3/100,000 during study period. The incidence of LAC increased with age before 70 years. The incidence of non-LAC increased with age. There were no significant differences in crude incidence of LAC between men and women (78.4/100,000 vs. 75.4/100,000). The incidence of non-LAC was significantly higher in men than in women (155/100,000 vs. 107/100,000, P < 0.001). The 28-day case fatality proportions were significantly lower in patients with LAC (0.5%) versus non-LAC (14.9%). One year after acute stroke onset, the survival rates between LAC and non-LAC were similar. CONCLUSION: LAC is a common stroke subtype in Northern China. Men or the elderly are more likely to have non-LAC. Long-term survival following LAC is similar to non-LAC patients.

Interventions for relieving pain associated with panretinal photocoagulation: a prospective randomized trial.

PURPOSE: To evaluate the efficacy of pain relief by oral diazepam, acetaminophen, mefenamic acid, intramuscular ketorolac tromethamine, and peribulbar anaesthesia in panretinal photocoagulation (PRP). METHODS: A total of 220 patients with proliferative diabetic retinopathy requiring PRP treatment were enrolled in this study. Before laser treatment, the patients were allocated randomly to one of eight groups: group 1: diazepam (n=22), group 2: acetaminophen (n=21), group 3: mefenamic acid (n=21), group 4: diazepam and acetaminophen (n=22), group 5: diazepam and mefenamic acid (n=22), group 6: peribulbar anaesthesia with lidocaine (n=23), group 7: intramuscular injection of ketorolac tromethamine (n=22), group 8: placebo (n=67). Pain after the laser treatment was assessed by a verbal descriptive scale. Blood pressure and heart rate were measured before and after laser treatment. RESULTS: Patients receiving peribulbar anaesthesia had a significantly lower pain score than the control group (P<0.0001). Additionally, the peribulbar anaesthesia-treated group had the significantly least PRP-associated rise in either systolic (P=0.043) or diastolic blood pressure rates (P=0.030). There were no significant differences in pain score using other anesthetic agents when compared with the control group. There were no significant changes in heart rate after PRP treatment. CONCLUSION: Peribulbar anaesthesia is effective in reducing pain and blood pressure increase after PRP treatment. Oral diazepam, mefenamic acid, and acetaminophen (either alone or in combination with each other) are not effective in preventing PRP treatment-associated pain. Intramuscular injection of ketorolac tromethamine is also not effective in reducing PRP-associated pain.

Purificación y caracterización parcial de una enzima dextranasa a partir de una cepa del hongo del género Penicillium / Purification and partial characterization of a destranase enzyme from a fungal strain of the genero Penicillium

Una fracción dextranasa (EC 3.2.1.11) excretada por un hongo del género Penicillium, fue purificada después de cinco días de inducción de la enzima en cultivo sumergido en agitación a 28-C. El crudo enzimático fue precipitado con 80

de sulfato de amonio, resuspendido en tampóm acetato y aplicado en cromatografía sucesivas de filtración por el gel e intercambio iónico. La fracción homogénea de dextrabasa está formada por dos bandas de proteinas superpuestas con un peso molecular aproximado de 67 000 Da, un nivel de glicosidación entre 15-18

y un punto isoeléctrico a pH 3,88. La actividad específica osciló entre 1 500 y 2 000 U/mg de proteína con un máximo de actividad a pH 5 (AU)