Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis.

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

Dark2Light: multi-stage progressive learning model for low-light image enhancement.

Due to severe noise and extremely low illuminance, restoring from low-light images to normal-light images remains challenging. Unpredictable noise can tangle the weak signals, making it difficult for models to learn signals from low-light images, while simply restoring the illumination can lead to noise amplification. To address this dilemma, we propose a multi-stage model that can progressively restore normal-light images from low-light images, namely Dark2Light. Within each stage, We divide the low-light image enhancement (LLIE) into two main problems: (1) illumination enhancement and (2) noise removal. Firstly, we convert the image space from sRGB to linear RGB to ensure that illumination enhancement is approximately linear, and design a contextual transformer block to conduct illumination enhancement in a coarse-to-fine manner. Secondly, a U-Net shaped denoising block is adopted for noise removal. Lastly, we design a dual-supervised attention block to facilitate progressive restoration and feature transfer. Extensive experimental results demonstrate that the proposed Dark2Light outperforms the state-of-the-art LLIE methods both quantitatively and qualitatively.

Parametric population pharmacokinetics of linezolid: A systematic review.

AIMS: Linezolid is often used for the infections caused by drug-resistant Gram-positive bacteria. Recent studies suggest that large between-subject variability (BSV) and within-subject variability could alter drug pharmacokinetics (PK) during linezolid therapy due to pathophysiological changes. This review synthesized information on linezolid population PK studies and summarized the significant covariates that influence linezolid PK. METHODS: A literature search was performed using PubMed, Web of Science and Embase from their inception to 30 September 2021. Published studies were included if they contained data analysing linezolid PK parameters in humans using a population approach with a nonlinear mixed-effects model. RESULTS: Twenty-five studies conducted in adults and five in paediatrics were included. One- and two-compartment models were the commonly used structural models for linezolid. Body size (weight, lean body weight and body surface area), creatinine clearance (CLcr) and age significantly influenced linezolid PK. The median clearance (CL) values (ranges) in infants (0.128 L/h/kg [0.121-0.135]] and children (0.107 L/h/kg [0.088-0.151]] were higher than in adults (0.098 L/h/kg [0.044-0.237]]. For patients with severe renal impairment (CLcr ≤ 30 mL/min), the CL was 37.2% (15.2-55.3%) lower than in patients with normal renal function. CONCLUSION: The optimal linezolid dosage should be adjusted based on the patient's body size, renal function and age. More studies are needed to explore the exact mechanism of linezolid elimination and evaluate the PK characteristics in paediatric patients.

Discovery of aryl sulfonamide-selective Nav1.7 inhibitors with a highly hydrophobic ethanoanthracene core.

Nav1.7 channels are mainly distributed in the peripheral nervous system. Blockade of Nav1.7 channels with small-molecule inhibitors in humans might provide pain relief without affecting the central nervous system. Based on the facts that many reported Nav1.7-selective inhibitors contain aryl sulfonamide fragments, as well as a tricyclic antidepressant, maprotiline, has been found to inhibit Nav1.7 channels, we designed and synthesized a series of compounds with ethanoanthracene and aryl sulfonamide moieties. Their inhibitory activity on sodium channels were detected with electrophysiological techniques. We found that compound 10o potently inhibited Nav1.7 channels stably expressed in HEK293 cells (IC50 = 0.64 ± 0.30 nmol/L) and displayed a high Nav1.7/Nav1.5 selectivity. In mouse small-sized dorsal root ganglion neurons, compound 10o (10, 100 nmol/L) dose-dependently decreased the sodium currents and dramatically suppressed depolarizing current-elicited neuronal discharge. Preliminary in vivo experiments showed that compound 10o possessed good analgesic activity: in a mouse visceral pain model, administration of compound 10o (30-100 mg/kg, i.p.) effectively and dose-dependently suppressed acetic acid-induced writhing.

Is a Lower Dose of Rivaroxaban Required for Asians? A Systematic Review of a Population Pharmacokinetics and Pharmacodynamics Analysis of Rivaroxaban.

Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required for Asians is still debatable. This review aimed to explore the potential ethnic difference in pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Asians and Caucasians. A systematic search was conducted and twenty-four studies were identified, of which 10 were conducted on Asian adults, 11 on predominantly Caucasian adults, and 3 on Caucasian pediatrics. The apparent clearance (CL/F) of rivaroxaban in Caucasian adults with non-valvular atrial fibrillation (6.45-7.64 L/h) was about 31-43% higher than that in Asians (4.46-5.98 L/h) taking 10~20 mg rivaroxaban every 24 h. Moreover, there was no obvious difference in CL/F among Japanese, Chinese, Thai, and Irani people. Regarding PK/PD relationship, prothrombin time was linked to rivaroxaban concentration in a linear or near-linear manner, and Factor Xa activity was linked with the Emax model. The exposure-response relationship was comparable between Asians and Caucasians. Renal function has a significant influence on CL/F, and no covariate was recognized for exposure-response relationship. In conclusion, a lower dose of rivaroxaban might be required for Asians, and further studies are warranted to verify this ethnic difference to facilitate optimal dosing regimens.

External evaluation of the predictive performance of published population pharmacokinetic models of linezolid in adult patients.

OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

Handling Delayed or Missed Dose of Antiseizure Medications: A Model-Informed Individual Remedial Dosing.

BACKGROUND AND OBJECTIVES: Delayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of 11 commonly used ASMs. METHODS: To explore remedial dosing regimens, Monte Carlo simulation was used based on previously identified and published population pharmacokinetic models. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients' demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were used to perform Monte Carlo simulation and recommend individual remedial regimens. RESULTS: The recommended remedial regimens were highly correlated with delayed time, scheduled dosing interval, and half-life of the ASM. Moreover, the optimal remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affects the clearance of the ASM, may also influence the remedial regimens. A web-based dashboard was developed to provide individualized remedial regimens for the delayed or missed dose, and a user-defined module with all parameters that could be defined flexibly by the user was also built. DISCUSSION: Monte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of ASMs in pediatric and adult patients with epilepsy.

Pressure-driven power generation and ion separation using a non-uniformly charged nanopore.

Due to its versatile potential applications, nanofluidic devices have drawn much attention of researches in various fields. Among these, pressure-driven power generation is considered as a candidate for the next generation alternative green energy source, and pressure-driven ion separation (nanofiltration) for desalination. Aiming to achieve a better performance in these two representative cases, a cylindrical nanopore having different types of non-uniform surface charge profile is adopted, and its performance under various conditions assessed. We show that lower the surface charge density near the nanopore inlet region can suppress the effect of ion concentration polarization (ICP) and improve the selectivity, thereby enhancing appreciably its power generation performance. For a fixed averaged surface charge density, if the bulk salt concentration is low, the higher the surface charge density near the nanopore openings, the better its performance. The degree of ICP can be alleviated by applying a sufficiently large pressure difference. Although previous studies showed that salt rejection is influenced significantly by the profile of the electric field inside a nanopore, we find that the electric field at nanopore openings also plays a role. Through choosing appropriately the surface charge profile, it is possible to solve the trade-off between rejection and flow rate.

Space charge modulation and ion current rectification of a cylindrical nanopore functionalized with polyelectrolyte brushes subject to an applied pH-gradient.

Considering versatile potential applications of bioinspired membranes, we simulate the electrokinetic behavior of a cylindrical nanopore, surface modified by a polyelectrolyte (PE) layer. Taking account of the effect of electroosmotic flow and an additionally applied pH gradient, the influences of the strength of the pH gradient, the PE layer thickness, the length of the nanopore and its radius on its conductance and ion current rectification (ICR) performance are assessed. We show that if pHU (the pH at the higher pH end of the nanopore) is fixed at 11 and pHL (the pH at the lower pH end of the nanopore) varies from 3 to 11, the rectification factor Rf has a local maximum occurring in 6 < pHL <8; the greater the magnitude of the applied potential bias |V| the smaller the pHL at which the local maximum occurs. The influence of the PE layer thickness on the nanopore rectification performance is important only if 5 < pHL <8, and the optimum performance is reached at a medium thick PE layer (ca. 3 nm). Possible mechanisms associated with the ion transport phenomenon under consideration are proposed and discussed in detail.

[Scraping needling technique combined with western medication for neurogenic tinnitus of kidney essence deficiency：a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of scraping needling technique combined with western medication and simple western medication for neurogenic tinnitus of kidney essence deficiency. METHODS: A total of 68 patients with neurogenic tinnitus of kidney essence deficiency were randomly divided into an observation group and a control group, 34 cases in each group. In the control group, oral methylcobalamin tablets were given, 0.5 mg each time, 3 times a day; oral flunarizine hydrochloride capsules were given before bed, 5 mg each time, once a day, 4 weeks in total. On the basis of the treatment as the control group, scraping needling technique was applied at Tinghui (GB 2), Yifeng (TE 17), Yangchi (TE 4) on the affected side and Shenshu (BL 23), Lieque (LU 7), 5 min each acupoint, once a day, 5 times a week for 4 weeks. Before treatment, 2, 4 weeks into treatment and 4 weeks after treatment (follow-up), the tinnitus severity score, tinnitus visual analogue scale (VAS) score and pure tone average (PTA) were observed, and the clinical efficacy was evaluated in the two groups. RESULTS: The tinnitus severity scores, VAS scores and PTA of each time point after treatment in the two groups were lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rates of each time point after treatment in the observation group were 50.0% (17/34), 79.4% (27/34), 79.4% (27/34), which were higher than 26.5% (9/34), 64.7% (22/34), 61.8% (21/34) in the control group (P<0.05). CONCLUSION: Scraping needling technique combined with western medication could improve tinnitus severity, tinnitus volume and hearing in patients with neurogenic tinnitus of kidney essence deficiency, and its curative effect is better than simple western medication.

Population pharmacokinetics of oxcarbazepine: a systematic review.

INTRODUCTION: Oxcarbazepine is commonly used as first-line treatment for partial and generalized tonic-clonic seizures. Owing to the high pharmacokinetic variability, several population pharmacokinetic models have been developed for oxcarbazepine to explore potential covariates that affect its pharmacokinetic variation. AREAS COVERED: This review summarizes the published population pharmacokinetic studies of oxcarbazepine in children and adults available in PubMed and Embase databases. The quality of the retrieved studies was evaluated, and significant covariates that may have an impact on the dosage regimen of oxcarbazepine were explored. EXPERT OPINION: The pharmacokinetics of oxcarbazepine was founded to be affected by body weight and co-administration with enzyme inducers. Pediatric patients require a higher dose per kilogram than adults because children generally have a higher clearance than adults. Moreover, to maintain the target concentration, patients co-administrate with enzyme inducers need a higher dose than monotherapy due to higher clearance in those patients. Because limited information is available for exposure-response relationship, additional pharmacokinetic/pharmacodynamics investigations of oxcarbazepine need to be conducted to optimize the dosage regimen in clinical practice.

Design and synthesis of biotin-tagged photoaffinity probes of jasmonates.

Jasmonates (JAs) are a class of oxylipin compounds that play diverse roles in plant defense and development. The F-box protein coronatine insensitive 1 (COI1) plays a crucial role in the JA signaling pathway. To determine whether COI1 binds directly to jasmonates, three biotin-tagged photoaffinity probes for JAs, a jasmonic acid photoaffinity probe (PAJA), a JAIle photoaffinity probe (PAJAIle), and a coronatine photoaffinity probe (PACOR), were designed and synthesized based on analysis of JA structure-activity relationships and molecular modeling of the interaction between COI1 and JAs. Among them, PACOR exhibited the most significant biological activity in inhibiting root growth, promoting accumulation of JA-responsive proteins, and triggering COI1-JAZ1 interaction in Arabidopsis seedlings. PACOR is an effective tool for elucidating the interaction between COI1 and JA.

[Clinicopathological characteristics of hereditary ovarian cancer syndrome].

OBJECTIVE: To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS). METHODS: From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). RESULTS: The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group. CONCLUSION: Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.

[The rule of metastatic pelvic lymph node distribution in patients with early stage cervical carcinoma].

OBJECTIVE: To investigate the distribution of metastatic pelvic lymph nodes in the women with early stage cervical carcinoma, and the feasibility of dividing these nodes into three stations in those patients. METHODS: (99m)Tc-DX of 2 ml was injected into the cervix to a depth of 5 to 10 mm at 3, 6, 9, 12 o'clock positions preoperatively in 196 patients with early stage cervical cancer. Pelvic lymphadenectomy and radical hysterectomy were performed in all patients. Pelvic lymph nodes were detected by gamma-probe. The sentinel lymph nodes (SLN) were determined if the radioactivity reached 5 times higher than that in the ipsilateral nodes. All resected pelvic lymph nodes were examined by histopathology with HE stained serial sections. RESULTS: Of the 196 patients, 41 were found to have metastasis in 83 lymph nodes. The metastatic rate was 78.3% (65/83) in the parametrial and obturator lymph nodes, 20.5% (17/83)in the internal and external iliac lymph nodes, 1.2% (1/83) in the commmon iliac lymph nodes. Of the 22 patients with metastatic parametrial lymph nodes, metastatic external iliac lymph nodes were detected in 5 patients, and metastatic internal iliac lymph nodes in 3 patients. Among the 19 patients with metastatic obturator lymph nodes, metastatic external iliac lymph nodes were found in 4 patients, and metastatic internal iliac lymph nodes in 3 cases. It was shown by Chi-sqare test that the metastases in parametrial and/or obturator lymph nodes were positively correlated with lymph node metastases in other pelvic sites. Eighty-one SLN were found to have metastasis. The metastatic rate of parametrial and obturator SLN was 79.0% (64/81) versus 21.0% (17/81) of internal and external iliac SLN. No statistically significant difference in 1- and 3-yr survival was observed between the groups with and without metastasis in parametrial and obturator lymph nodes, while the 5-yr survival rate in the patients without metastatic lymph node was 93.2%, significantly higher than that of patients with lymphatic metastasis (65.1%). CONCLUSION: It is feasible for cervical cancer to divide the pelvic lymph nodes into three levels. The level I lymph nodes consist of parametrial and obturator lymph nodes. Internal and external iliac lymph nodes can be considered as level II lymph nodes, and the common iliac and inguinal lymph nodes as level III nodes. A rational treatment plan can be made according to the distribution of metastatic pelvic lymph nodes.

CAFs enhance paclitaxel resistance by inducing EMT through the IL­6/JAK2/STAT3 pathway.

Carcinoma­associated fibroblasts (CAFs) are the major components of mesenchymal cells in the inflammatory tumor microenvironment. They are involved in epithelial­mesenchymal transition (EMT) and chemotherapy resistance by directly contacting with cancer cells or secretory cytokines. In the present study, we examined the role of CAFs in the induction of EMT in ovarian cancer. Primary ovarian cancer cells, CAFs and normal fibroblasts (NFs) were isolated from fresh cancer tissue and cultured for immunohistochemistry studies. Enzyme­linked immunosorbent assay (ELISA) was used to detect the expression of IL­6 in the culture supernatants of these cells. The expression of IL­6 at the mRNA level was examined by RT­PCR. The expression of IL­6 at the protein level in ovarian cancer tissues was determined using an immunofluorescence assay in both tissue sections and cell lobes. OVCAR3 cells were treated with the culture supernatants collected from CAFs and NFs. IL­6 monoclonal antibody (mAb) was employed to neutralize IL­6. The expression of phosphorylated STAT3 was assessed. Changes in EMT, proliferation, invasion and proapoptotic protein expression were also examined. Flow cytometry was performed to detect the changes in apoptosis resistance of OVCAR3 cells. The JAK2/STAT3 pathway­specific inhibitor AG490 was used to block this pathway and the ß­TGF inhibitor was used to inhibit EMT. The clinical data of patients treated in our hospital were collected between January 1st, 2009 and June 30th, 2013. The expression of interstitial IL­6 in paraffin­embedded tissues was detected by immunohistochemistry. The relationship between the expression of interstitial IL­6 and the treatment response was examined by linear regression and multiple linear regression analyses. We found that CAFs were the main source of IL­6 in ovarian cancer tissue. CAFs promoted the phosphorylation of STAT3 in ovarian cancer and enhanced the proliferation, invasion and EMT. Enhanced EMT may lead to apoptosis resistance, inhibitory expression of pro­apoptotic proteins and paclitaxel resistance. A total of 255 patients were enrolled in this retrospective study. Univariate and multivariate analyses revealed that age, CA125, interstitial IL­6 expression and cytoreduction satisfaction were closely related to the sensitivity of the TP (docetaxel plus cisplatin or carbopatin) regimen in ovarian cancer (P<0.05). These results demonstrated that CAFs highly secreted IL­6 and promoted ß­TGF­mediated EMT in ovarian cancer via the JAK2/STAT3 pathway, leading to inhibited apoptosis and subsequent paclitaxel resistance. Therefore, CAFs may be a new therapeutic target for the treatment of ovarian cancer.

[Effect of Acupuncture at "Taichong"(LR 3) and "Neiguan"(PC 6) on Blood Pressure and Contents of Aspartic Acid and Glutamic Acid in the Rostral Ventrolateral Medulla in Spontaneous Hypertension Rats].

OBJECTIVE: To explore the potential mechanism of acupuncture stimulation of "Taichong" (LR 3) and "Neiguan" (PC 6) in spontaneous hypertension rats (SHR) by investigating its effects on blood pressure and contents of aspartic acid(Asp) and glutamic acid (Glu) in the rostral ventrolateral medulla (RVLM) region. METHODS: A total of 75 SHR were randomized into model group, Taichong (LR 3) group, Neiguan (PC 6) group, LR 3+non-acupoint group and LR 3 + PC 6 group (n=15 rats in each group), and 15 Wistar rats of the same age were used as the normal control group. The filiform needles were inserted into the abovementioned acupoints and non-acupoint, twirled for a while and then retained for 30 min. The treatment was conducted once per day, 15 times in total. The rats' tail blood pressure was examined on day 1, 3, 7 and 15 after acupuncture treatment by using a non-invasive blood pressure monitor. At the end of experiment, the contents of Asp and Glu in the RVLM were detected by high-performance liquid chromatography with UV technique. RESULTS: On day 1, 3, 7 and 15 after the acupuncture treatment, the raised systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 groups were all decreased significantly compared with the model group (P<0.05). On day 15, the effect of the LR 3 + PC 6 group was significantly superior to that of the LR 3, PC 6, and LR 3 + non-acupoint groups in reducing the levels of SBP, DBP, and MBP (P<0.05).Compared with the normal control group, the contents of Asp and Glu in RVLM were significantly higher in the model group (P<0.05). After acupuncture intervention, both Asp and Glu levels in the PC 6, LR 3, LR 3 + non-acupoint, and LR 3 + PC 6 groups were markedly lower in comparison with the model group (P<0.05), and those of the LR 3 + PC 6 group were notably lower than those in the LR 3 and PC 6 groups (P<0.05). CONCLUSIONS: Acupuncture stimulation of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 (in particular) is effective in lowering blood pressure in spontaneous hypertension rats, which may be associated with its effects in lowering Asp and Glu contents in RVLM.

Peripheral platelet/lymphocyte ratio predicts lymph node metastasis and acts as a superior prognostic factor for cervical cancer when combined with neutrophil: Lymphocyte.

Inflammation-based indicators such as neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), and platelet/lymphocyte ratio (PLR) have been reported to possess significant predictive value for several types of cancer. We investigated the predictive value of these 3 biomarkers on lymph node metastasis (LNM) and clinical outcome in patients with stage Ib1-IIa cervical cancer undergoing radical surgery.A total of 407 patients with FIGO stage Ib1-IIa cervical cancer, who underwent radical surgery between January 2006 and December 2009 at the Department of Gynecological and Oncology of Shandong Cancer Hospital Affiliated to Shandong University were recruited. Binary logistic regression analysis was performed to determine the relationship between PLR, NLR, dNLR, and LNM. Multivariate Cox regression analysis was performed to determine the association between the 3 indices and recurrence-free survival (RFS) and overall survival (OS).Optimal cut-off values for the 3 indices were determined by applying receiver operating curve (ROC) analysis. Univariate and binary logistic regression analyses both indicate that PLR was significantly associated with increased LNM (P < 0.05). In the multivariate survival analysis, increased preoperative PLR and NLR were significantly associated with reduced RFS (P = 0.001 and P = 0.002, respectively), whereas a combination of both PLR and NLR revealed a more significant association with reduced RFS (P < 0.001). Furthermore, increased preoperative PLR and NLR were significantly associated with reduced OS (P = 0.007 and P = 0.009, respectively), whereas the combined use of PLR and NLR revealed a more significant association with reduced OS (P = 0.003).PLR is an independent risk factor for increased LNM and clinical outcome in patients with stage Ib1-IIa cervical cancer. A combination of PLR and NLR may enable better risk stratification for predicting survival.

MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells.

Ovarian cancer is a leading cause of malignant gynecological tumor-related mortality among women. The treatment of ovarian cancer patients continues to be challenging. MicroRNA­106a (miR­106a) is widely expressed in diverse human tumors. In the present study, we investigated the biological and pathological roles of miR-106a in ovarian cancers. We found that miR-106a expression was significantly increased in primary ovarian cancer tissues and ovarian cancer cells compared with the level in normal tissues. Ectopic expression of an miR-106a inhibitor attenuated ovarian cancer cell proliferation and invasion. miR-106a promoted the growth and invasion of SKOV3 cells by targeting phosphatase and tensin homolog (PTEN). Furthermore, the present study revealed that IL-6 inhibited miR-106a expression by activating STAT3. Tocilizumab, a humanized anti-human IL-6R antibody, that competitively inhibits IL-6/IL-6R signaling, did not inhibit the proliferation and invasion of SKOV3 cells. In conclusion, our studies revealed that miR-106a was significantly increased in the ovarian cancer tissues and cell lines. Downregulation of the expression of miR-106a inhibited cell growth and metastasis of ovarian cancer cells. Together, the present study suggests that miR­106a acts as an oncogene in ovarian cancers.