GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization.

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.

Multislice spiral CT images combined with CEA and lymphocyte-to-neutrophil ratio predict recurrence and post-operative metastasis of rectal cancer.

To explore the early predictors of post-operative recurrence and metastasis of rectal cancer, analyse the associated risk, and construct a model. Retrospective collection. Four hundred patients with rectal cancer underwent surgical resection and pathological diagnosis from September 2013 to September 2014. During the post-operative period, the patients were tested by imaging examination, serum tumour markers, and routine blood follow-up for at least 3 years. Preoperative CT examination of tumour size, lymphocyte-to-neutrophil ratio, and CEA were significant biomarkers for predicting recurrence and/or metastasis of post-operative rectal cancer. The stratified threshold of the lesion size cut-off point in CT images of patients with rectal cancer was 18.75 cm3, the cut-off point value of the lymphocyte-to-neutrophil ratio was 0.33, and the CEA cut-off point value was 16.97 ng/ml. We used the cut-off point to perform stratified survival analysis to obtain two K-M curves and conduct a log-rank test. The Cox multivariate risk regression results were as follows: preoperative CT images of lesion size, lymphocyte-to-neutrophil ratio, and CEA. The AUC of the normogram model for the prediction of post-operative recurrence and metastasis of rectal cancer is 0.939. Preoperative CT examination of tumour size can predict post-operative recurrence and metastasis of rectal cancer and can be used to analyse its risk. The lymphocyte-to-neutrophil ratio and CEA can also predict post-operative tumour recurrence and metastasis risk.

[Impact of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow on dysmenorrhea patients of cold stagnation and blood stasis syndrome with Dingkun Dan].

This research apply Dingkun Dan to treat patients with dysmenorrhea of cold stagnation and blood stasis syndrome. This study observed its effectiveness and safety of the treatment of the disease and its influence on the serum prostaglandin F2α, endothefin, pulsatility index and resistant index of uterine artery blood, to explore the possible mechanism of effect of Dingkun Dan in the treatment of dysmenorrhea and provide scientific basis for clinical application. The 75 patients with dysmenorrhea of cold stagnation and blood stasis who met the inclusion criteria, were divided into treatment group (n=37) and control group (n=38) by using random number remainder grouping method. In the treatment group patients were treated with Dingkun Dan, the other group were given Fuke Zaizao Jiaonang. Two groups have same time to take the medicine, three days prior to the menstruation for ten days. Medication for three menstrual cycles was seen as a course of treatment. To observe and compare the two groups of patients before and after treatment VAS score, syndrome integral, serum levels of prostaglandin F2α and endothelin, pulsation index and resistance index of uterine artery blood flow and related safety index changes. Finally makes statistical analysis. It has been identified that, Treatment group and control group can reduce pain symptom of dysmenorrhea patients and improve the syndromes scores, compare with control group, effect of the treatment group is more significant(P<0.01). VAS pain curative effect: the treatment group and control group total effective rate respectively were, 97.22%, 69.44%, markedly effective rate were 83.33%, 30.56%, comparison between two groups, treatment group is better than that of control group(P＜0.01). Syndromes curative effect: the treatment group and control group total effective rate respectively were 97.22%, 94.44%, markedly effective rate was 66.67%, 2.78%, respectively. The comparison between two groups, the total effective rate has no obvious difference, but markedly effective rate of treatment group is better than that of control group(P＜0.01). The treatment group can significantly reduce the patients' serum level of prostaglandin F2α(P<0.01), but no obvious difference was found in the control group before and after treatment. Both groups can significantly reduce the serum level of endothelin(P<0.01), comparison between two groups, the treatment group is more significant(P<0.01).Both treatment group and control group were significantly lower left and right pulsation index and resistance index of uterus artery blood flow(P<0.01). Between groups to compare the effect, the treatment group is more significant(P<0.01). Both treatment group and control group in the security check before and after treatment found no significant anomalies. Dingkun Dan in treating dysmenorrhea with cold stagnation and blood stasis syndrome seems to have remarkable clinical curative effect and safety, which may be achieved by significantly reducing the serum level of prostaglandin F2αand endothefin of the patients, and reducing the pulsation index and resistance index of uterine artery blood flow of the patients, to improve uterine artery condition of blood, and correcting local tissue ischemia to relieve pain.

Effects of tetrahydroxystilbene glucoside on mouse liver cytochrome P450 enzyme expressions.

1. To investigate the effects of tetrahydroxystilbene glucoside (TSG), the main active component of Polygonum multiflorum, on mouse liver cytochrome P450 (Cyp) enzyme protein expressions. Male mice were randomly divided into the control, TSG low (10 mg/kg) and high dose (40 mg/kg) groups. After TSG intragastrical administration for 3, 5 and 7 d, mice were sacrificed and the mouse body and liver weight were detected. The Cyp enzymes and various transcription factors such as AhR, PXR and PPARα protein expressions in mouse livers were measured by Western blotting assay. 2. No significant difference of mouse body and liver weight between the control and TSG treatment groups was detected. Additionally, TSG decreased Cyp1a2 and Cyp2e1 protein expressions after TSG treatment for 3, 5 and 7 d, respectively. Moreover, TSG suppressed Cyp3a11 protein expression after TSG treatment for 5 and 7 d. Furthermore, TSG high dose inhibited AhR and PXR protein expressions after TSG treatment for 5 and 7 d, while both TSG low dose and high dose obviously decreased PPARα protein level from TSG treatment for 3 d. 3. TSG has inhibitory effects on mouse liver Cyp1a2, Cyp2e1 and Cyp3a11 protein expressions through the suppression of AhR, PXR and PPARα activation.

[Qualitative Determination of Organic Vapour Using Violet and Visible Spectrum].

Vapours of organic matters were determined qualitatively employed with ultraviolet-visible absorption spectroscopy. Vapours of organic matters were detected using ultraviolet-visible spectrophotometer employing polyethylene film as medium, the ultraviolet and visible absorption spectra of vegetable oil vapours of soybean oil, sunflower seed oil, peanut oil, rapeseed oil, sesame oil, cotton seed oil, tung tree seed oil, and organic compound vapours of acetone, ethyl acetate, 95% ethanol, glacial acetic acid were obtained. Experimental results showed that spectra of the vegetable oil vapour and the organic compound vapour could be obtained commendably, since ultra violet and visible spectrum of polyethylene film could be deducted by spectrograph zero setting. Different kinds of vegetable oils could been distinguished commendably in the spectra since the λ(max), λ(min), number of absorption peak, position, inflection point in the ultra violet and visible spectra obtained from the vapours of the vegetable oils were all inconsistent, and the vapours of organic compounds were also determined perfectly. The method had a good reproducibility, the ultraviolet and visible absorption spectra of the vapours of sunflower seed oil in 10 times determination were absolutely the same. The experimental result indicated that polyethylene film as a kind of medium could be used for qualitative analysis of ultraviolet and visible absorption spectroscopy. The method for determination of the vapours of the vegetable oils and organic compounds had the peculiarities of fast speed analysis, well reproducibility, accuracy and reliability and low cost, and so on. Ultraviolet and visible absorption spectrum of organic vapour could provide feature information of material vapour and structural information of organic compound, and provide a novel test method for identifying vapour of compound and organic matter.

[Analysis of questionnaire and clinical characteristics of 2,000 cases of dysmenorrheal].

Through the questionnaire survey of 2,000 patients with dysmenorrhea, the clinical characteristics of dysmenorrhea were investigated, and the reference basis for preventing and controlling dysmenorrhea was provided. The results found that the age of menarche, short menstrual cycle, by volume, long period of time has no obvious relationship with the occurrence of dysmenorrhea. Dysmenorrhea main influence factors to feel cold; syndrome (symptoms) characteristics for the actual situation inclusions mainly, with severity, deficiency symptoms more obvious; in different degrees of dysmenorrhea, frequency of belly chills symptoms appear most, and cold coagulation and blood stasis syndrome (symptoms) appear higher frequency; The type of cold coagulation and blood stasis dysmenorrhea was 53.2%. Dysmenorrhea measures to select bed rest most, accounting for 79.6%. For severe dysmenorrhea in patients with drug choice to traditional Chinese combined with western medicine accounted for 43.4%. Selection of Chinese medicine formulations in patients with dysmenorrhea Decoction formulation accounted for the most 26.5%. The survey results, to avoid cold and have a positive effect on the prevention of dysmenorrhea, dysmenorrhea treatment should pay attention to warming channels to dispel cold.

Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer prognosis and therapeutics.

Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor progression and oncogenesis. The aim of this study was to investigate the role of USP22 and the association with its potential targets in patients with cervical cancer. To our knowledge, this is the first study that determines the relationship between USP22 expression and clinicopathological significance in cervical cancer. The immunohistochemistry results showed that USP22 protein was overexpressed in cervical cancer samples compared with normal cervical tissues (P < 0.001). Moreover, clinicopathological analysis showed that USP22 expression was highly related to International Federation of Gynecology and Obstetrics stage, Ki67, lymph node metastasis, and histology grade. The results of Kaplan-Meier analysis indicated that patients with high USP22 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients with low expression of USP22 (P < 0.001). Multivariate Cox regression analysis revealed that USP22 expression status was an independent prognostic marker for both OS and DFS of patients with cervical cancer. It is suggested that USP22 overexpression may be associated with poor prognosis in cervical cancer. It may represent a novel prognostic biomarker or a target for improving the treatment efficiency of patients with cervical cancer.

Role of ZIC1 methylation in hepatocellular carcinoma and its clinical significance.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. The zinc finger of the cerebellum (ZIC1) gene is a novel tumor suppressor gene that plays a crucial role in vertebrate development. Altered expression of ZIC1 is observed in various types of human cancers. The aims of the present study were to investigate the methylation status of ZIC1 in HCC and evaluate its clinical implication. The methylation status of ZIC1 was analyzed in 132 pairs of HCC and corresponding noncancerous tissues by methylation-specific polymerase chain reaction (PCR) (MSP). The expression of ZIC1 messenger RNA (mRNA) in HCC tissues was examined by real-time PCR. Methylation frequency of ZIC1 in HCC was significantly higher than that in the corresponding noncancerous tissues (P < 0.001), and it was correlated with tumor size (P = 0.022), histological differentiation (P = 0.033), and tumor stage (P = 0.009). The downregulation of the ZIC1 mRNA expression in HCC was correlated with the ZIC1 methylation (P < 0.001). The patients with methylated ZIC1 had a poorer overall survival than those without methylated ZIC1 (P < 0.001). Taken together, our results suggested that the hypermethylation may lead to promoter silencing of ZIC1 mRNA and associated with poor survival in HCC. Overall, aberrant methylation is an important mechanism for ZIC1 inactivation in HCC, and ZIC1 methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release.

Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson's disease (PD). Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA) neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1) resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2) the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3) resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4) resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.

[Analysis of clinical and laboratory characteristics and survival with hairy cell leukemia].

OBJECTIVE: To explore the clinical and laboratory characteristics and survival of Chinese patients with hairy cell leukemia (HCL). METHODS: A total of 30 HCL patients from August 1990 to March 2012 were retrospectively analyzed. RESULTS: There were 22 cases with classical HCL (HCL-C) and 8 with variant HCL (HCL-V). Splenomegaly was the most common physical finding. Leukocytosis was found in all cases of HCL-V. But pancytopenia only accounted for 36.4% (8/22) in HCL-C. And 3/5 of HCL-V had abnormal chromosome karyotypes. Ribosomal-lamellae complexes (RLC) were found only in about 3/12 of HCL cases. Chemotherapy regimens including purine nucleoside analogues achieved a better complete remission (CR) rate than other regimens (3/4 vs 1/18, P = 0.012) in HCL-C. The median follow-up period was 27 (1 - 142) months. There was no follow-up loss. Eleven cases progressed and 6 died. The median overall survival (OS) was not reached. And the 1, 3, 6-year OS rates were 84%, 78% and 58% respectively. The median progression-free survival (PFS) was (63 ± 24) months and the 1, 2, 5-year PFS rates were 86%, 72% and 44% respectively. The median PFS of HCL-V was significant shorter than HCL-C ((23 ± 3) vs (78 ± 12) months, P = 0.014). In HCL-C group, fever (P = 0.038) and anemia (P = 0.000) at diagnosis were poor prognostic factors. But purine nucleoside analogues made no significant difference in PFS. CONCLUSIONS: Pancytopenia is infrequent in Chinese HCL patients. And classical RLC is rare under electron microscope. Purine nucleoside analogues may achieve a better CR rate, but fail to improve PFS rate. As compared with HCL-C, HCL-V is common with genetic abnormalities and has a worse prognosis with a shorter PFS.

Mechanism of Thymus Rejuvenation in Elderly Macaques.

Senile thymus atrophy is an important factor leading to decreased immune function. Repairing the atrophic thymus tissue structure, rebuilding immune function, and replenishing the number of exogenous stem cells may be ideal methods. In this study, bone marrow mesenchymal stem cells were intravenously infused into elderly macaques. We found that thymus volume was substantially increased, some thymus tissue regeneration was observed, the degree of thymus tissue fibrosis decreased, collagen fiber deposition decreased, cortical and medulla structures emerged gradually, the number of apoptotic cells decreased significantly, and the expression of apoptosis-related proteins decreased. For the effects of stem cell therapy on aging-related genes, we performed transcriptomic analysis of thymus tissue. The results show the expression pattern of the tissue transcriptome tended to be similar to the thymus expression pattern in young macaques compared with the elderly group, reverse aging-related proteins. Based on the results, it is suggested that stem cell therapy is an ideal method to prevent or reverse the aging of the thymus.

[Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders].

OBJECTIVE: To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders. METHODS: Peripheral blood samples (n = 78) and bone marrow samples (n = 9) were collected from patients with chronic lymphocytic leukemia (CLL, n = 53), mantle cell lymphoma (MCL, n = 13), splenic marginal zone lymphoma (SMZL, n = 9) and healthy donors (n = 12) at our hospital from 2003 to 2010. Mononuclear cells were isolated and B cells purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and the expression of microRNA-223 measured by TaqMan microRNA quantitative polymerase chain reaction (PCR). The clinical data of these patients were collected and their outcomes analyzed with SPSS 16.0 software. RESULTS: (1) The levels of microRNA-223 in CLL, MCL and SMZL were 4.58 ± 0.62, 4.03 ± 0.54 and 4.63 ± 0.57 respectively. And they were significantly lower than that in normal B cells (5.69 ± 0.60, P < 0.01). The expression of microRNA-223 decreased significantly in MCL versus CLL and SMZL (P < 0.05). There was no statistical difference between CLL and SMZL (P > 0.05). (2) The down-regulation of microRNA-223 was associated with disease aggressiveness in CLL. Patients with unmutated immunoglobulin heavy chain variable region (IgVH) expressed significantly a lower level of microRNA-223 (4.05 ± 0.69 vs 4.67 ± 0.51, P = 0.003). In 13q-negative patients, the expression of microRNA-223 decreased more significantly than that in 13q-positive patients (4.25 ± 0.67 vs 4.76 ± 0.45, P = 0.044). (3) Using receiver operating characteristic (ROC) curve analysis, the microRNA-223 cutoffs were defined according to the IgVH mutational status. The patients were divided into the positive and negative subgroups. The median progression-free survival (PFS) of microRNA-223 positive patient subgroup was 48 months. It was significantly longer than the negative subgroup (P = 0.001). In the microRNA-223 positive subgroup, no patient died at the end of follow-up. CONCLUSIONS: MicroRNA-223 may play an important role in the pathogenesis of B lymphoproliferative disorders. The down-regulation of microRNA-223 is associated with disease aggressiveness and poor prognostic factors in CLL. It may become a new reliable prognostic predictor.

Effects of different implant surface properties on the biological behavior of Schwann cells.

OBJECTIVES: This study investigated the effects of different implant surface properties on the biological behavior of Schwann cells. METHODS: Schwann cells (SCs) were cultured on three types of implant surfaces including smooth polished (SMO), sand-blasted, large grit, acid-etched (SLA), and chemically-modified SLA (modSLA). At different time points, the morphology and adhesion of SCs on the implant surfaces were observed by scanning electron microscope. Cell proliferation activity was detected by MTT method. The expression levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were detected by enzyme-linked immunosorbent assay. Changes in the mRNA levels of NGF and BDNF were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: SCs adhered, stretched, and proliferated well on the three types of implant surfaces. On the 3rd, 5th, and 7th days, the OD values of the SMO group were higher than those of the SLA group and the modSLA group, and the difference was statistically significant (P<0.05). On the 3rd day, the expression and mRNA levels of NGF and BDNF in the SLA group and the modSLA group were higher than those in the SMO group (P<0.05); in particular, the levels in the modSLA group were higher than those in the SLA group (P<0.05). CONCLUSIONS: Different implant surface properties have different effects on the biological behavior of SCs. Proliferation of SCs is significantly promoted by smooth surface, while secretion and gene expression of neurotrophic factors are significantly promoted by modSLA surface at early stage.

The effects of BMMSC treatment on lung tissue degeneration in elderly macaques.

BACKGROUND: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments. METHODS: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration. RESULTS: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05). CONCLUSIONS: BMMSC treatment inhibited age-associated lung tissue degeneration.

Screening of sleep assisting drug candidates with a Drosophila model.

Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep. We applied a daytime light-deprivation protocol (DD) mimicking jet-lag to screen drugs that alleviate sleep deprivation. Characteristically, classical sleep-aid compounds exhibited different forms of influence: phenobarbital and pentobarbital modified total sleep time, while melatonin only shortened the latency to sleep. Such results construct the basis for further research on sleep benefits in other treatments in Drosophila. We screened seven herb extracts, and found very diverse results regarding their effect on sleep regulation. For instance, Panax notoginseng and Withania somnifera extracts displayed potent influence on total sleep time, while Melissa officinalis increased the number of sleep episodes. By comparing these treatments, we were able to rank drug potency in different aspects of sleep regulation. Notably, we also confirmed the presence of sleep difficulties in a Drosophila Alzheimer's disease (AD) model with an overexpression of human Abeta, and recognized clear differences between the portfolios of drug screening effects in AD flies and in the control group. Overall, potential drug candidates and receipts for sleep problems can be identified separately for normal and AD Drosophila populations, outlining Drosophila's potential in drug screening tests in other populations if combined with the use of other genetic disease tools.

[Effects of platelet-derived growth factor on nerve regeneration around implant in rats].

OBJECTIVE: To investigate the effect of platelet-derived growth factor (PDGF) on nerve regeneration in peri-implant tissues. METHODS: SD rats with implants in their femurs were injected with PDGF solution. The effects of PDGF on nerve regeneration in peri-implant tissues were analyzed by immunohistochemical staining. RESULTS: PDGF increased the number of nerve fibers in peri-implant tissues at early stage. PDGF had no significant effect on the number of nerve fibers in peri-implant tissues at late stage. Moreover, these nerves had a typical structure of peripheral nerve fibers. CONCLUSIONS: PDGF can promote nerve regeneration in peri-implant tissues at early stage. This study provided a certain experimental basis for the clinical application of PDGF to promote nerve regeneration and further improve the sensory function of the implant.

Retrospective analysis of cervical cancer and precancerous lesions in patients with atypical squamous cells of undetermined significance in China.

Atypical squamous cells of undetermined significance (ASCUS) are the most common cytological abnormality of all smear test. No study has demonstrated the prevalence of cervical cancer or its precursor in Chinese patients with ASCUS. This study aims to investigate the prevalence of cervical intraepithelial neoplasia 1 or worse (CIN1+) and CIN3 or worse (CIN3+) in patients with ASCUS in China to provide insight into appropriate management for Chinese health care.In a retrospective cross-sectional study, patients who underwent liquid-based thin layer cytology and human papillomavirus (HPV) co-testing at the Peking Union Medical College Hospital between January 2014 and January 2017, and had ASCUS results on liquid-based thin layer cytology test and underwent follow-up and colposcopic biopsy were included. Age, HPV DNA test, and pathological outcomes were assessed.One hundred forty-four patients with ASCUS and positive HPV test results were included. In the 3-year follow-up, 23 (16.0%) patients had CIN1, 28 (19.4%) had CIN2, and 17 (11.8%) had CIN3 or carcinoma in situ. The risk of CIN3+ was significantly higher in those older than 60 years (42.8%, P = .005), whereas the CIN1+ prevalence displayed no significant difference between age groups. Both hybrid Capture II (HC II) value and cytopathological description of HPV infection showed no statistically significant correlation with CIN1+ or CIN3+.Patients with HPV-positive ASCUS who were older than 60 years had a significantly higher risk of CIN3+, and clinicians should pay more attention to them. Both HC II value and cytopathological description of HPV infection showed no significant correlation with CIN1+ or CIN3+.

General anesthesia combined with epidural anesthesia maintaining appropriate anesthesia depth may protect excessive production of inflammatory cytokines and stress hormones in colon cancer patients during and after surgery.

The purpose of this study was to investigate the influences of varied anesthetic methods and depths on inflammatory cytokines and stress hormone levels in radical operation among colon cancer patients during perioperative period.A total of 120 patients were collected in the study and randomly divided into 4 groups, A: general anesthesia + Narcotrend D1, B: general anesthesia + Narcotrend D2, C: general anesthesia + epidural anesthesia + Narcotrend D1, D: general anesthesia + epidural anesthesia + Narcotrend D2. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, cortisol (Cor), adrenocorticotropic hormone (ACTH), and endothelin-1 (ET-1) were measured adopting commercial kits before anesthesia (T0), 4 hours after surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3).There was no significant difference in basic clinical characteristics among the groups. In comparison with group A, B and C, group D showed significantly lower levels of TNF-α, IL-6, IL-10, Cor, ACTH, and ET-1 at T1 and T2 (all, P < .05). Significantly higher levels of TNF-α, IL-6, IL-10, Cor, and ACTH were detected at T1 and T2 than those at T0 (all, P < .05), whereas, at T3, the levels of inflammatory cytokines and stress hormones were all decreased near to preoperation ones.General anesthesia combined with epidural anesthesia at Narcotrend D2 depth plays an important role in reducing immune and stress response in patients with colon cancer from surgery to 24 hours after surgery.

The transcriptional profiles and functional implications of long non-coding RNAs in the unfolded protein response.

The unfolded protein response (UPR) is activated, when the folding capacity is compromised in the endoplasmic reticulum (ER). To date, most studies focused on the coding genes and microRNAs in UPR. Other non-coding RNAs affected by UPR and their roles in UPR have not been systematically studied. Long noncoding RNAs (lncRNAs) are increasingly recognized as powerful epigenetic regulators. In this study, we transcriptomically profiled the lncRNAs and mRNAs from mouse embryonic fibroblasts under ER stress, and identified many differentially expressed lncRNAs and mRNAs. Genomic location and mRNA-lncRNA co-expression analyses predicted a number of lncRNAs, which potentially regulate the expression of UPR genes. In particular, FR229754, an exonic sense lncRNA, is significantly up-regulated in UPR. FR229754 overlaps with Sel1l, and their expressions correlated with each other. Sel1l is involved in the ER-associated protein degradation. Silencing of FR229754 did not much affect the expression of Sel1l, but markedly reduced the levels of BiP/GRP78/Hspa5, a major ER chaperon up-regulated in UPR. Probing with pathway-specific inhibitors showed that up-regulation of FR229754 and Sel1 depended on the activation of PERK. Together, our study identified a number of candidate lncRNAs and paved the way for future characterization of their functions in UPR.

[Effects of co-administration of growth hormone(GH) and aspirin to women during in vitro fertilization and embryo transfer (IVF-ET) cycles].

OBJECTIVE: To study the effects of the co-administration of growth hormone (GH) and aspirin to women with suboptimal response to GnRHa/FSH hyperstimulation protocol during in vitro fertilization and embryo transfer (IVF-ET) cycles. METHODS: Forty cases of poor ovarian response in previous IVF-ET cycles were randomly divided into 2 groups: the studied group of GH and aspirin (n = 20), and the control group without GH or aspirin (n = 20). RESULTS: The co-administration of GH and aspirin significantly increased the rates of retrieved oocytes (P < 0.01), promoted the maturation of oocytes (P < 0.01) and improve the fertilization rates (P < 0.05). However, there were no statistically differences between the two groups in the number of replaced embryos (P > 0.05) and the pregnancy rate (P > 0.05). CONCLUSION: The co-administration of GH and aspirin to poor ovarian responders is effective to increase the rates of retrieved oocytes, promote the maturation of oocytes and improve the fertilization rate in IVF-ET.