LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.

Establishment of the prediction models of malignant brain edema after vascular recanalization in anterior circulation acute large vascular occlusion stroke / 国际外科学杂志

Objective:Based on Logistic regression and XGBoost algorithm, the prediction model of malignant brain edema (MBE) after vascular recanalization of anterior circulation acute great vessel occlusive stroke (ALVOS) was constructed, and the prediction performance was compared.Methods:A retrospective selection of 382 patients with anterior circulation ALVOS who underwent early endovascular treatment (EVT) in our hospital from March 2014 to June 2020 and successfully recanalized the occluded blood vessel was selected. The patients were divided into the training group ( n=267) and the test group ( n=115) according to the ratio of 7∶3 by the random number table method. According to whether the patients had MBE after successful recanalization of the occluded blood vessels, the training group was divided into the MBE group ( n=41) and non-MBE group ( n=226). The baseline data, treatment and brain computed tomography perfusion(CTP) results of MBE group and non-MBE group in training group and test group were compared respectively, including age, admission score of National Institutes of Health Stroke Scale (NIHSS), grade of cerebral collateral circulation, cerebral blood volume, and so on. Logistic regression model and XGBoost algorithm model were used to screen the predictors of MBE in ALVOS patients with occluded vessels successfully recanalized, and the discrimination and calibration of the two models were compared. The measurement data conforming to the normal distribution were expressed as mean ± standard deviation ( ± s), and the independent sample t test was used for comparison between the two groups. Non-normally distributed measurement data were represented by M ( Q1, Q3), using independent sample Mann-Whitney U test. The chi-square test was used to compare the count data between groups. Results:There was no significant difference in baseline data, treatment status, and cranial computed tomography perfusion (CTP) imaging results of the training group and the test group ( P>0.05). The age, admission systolic blood pressure, admission NIHSS score, proportion of hypertension, proportion of cerebral collateral circulation 0-2, proportion of thrombus removal times> 3 times, time from onset to recanalization, and cerebral blood volume (CBV) of MBE group were (68.95±8.04) years old, (146.71±22.73) mmHg, 17(13, 21) min, 87.80%, 82.93%, 68.29%, (365.64±87.83) min, (32.56±5.73) mL/100 g, obvious higher than the non-MBE group [(60.27±7.13) years old, (137.92±19.58) mmHg, 14(10, 18) points, 73.01%, 60.62%, 2.65%, (307.59±74.05) min, (27.49±5.46) mL/100 g] ( P<0.05). The results of Logistic regression model showed that age, NIHSS on admission, grade of cerebral collateral circulation, times of thrombectomy and time from onset to recanalization were the predictors of MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS ( P<0.05). The top five important feature scores of XGBoost algorithm model were cerebral collateral circulation classification 34, embolectomy times 27, onset to vascular recanalization time 25, admission NIHSS score 22, age 16.In the training set, the area under the curve of the Logistic regression model was 0.816(95% CI: 0.749-0.883), and the Hosmer-Lemeshow test showed that χ2=1.547, P=0.438. The area under the curve of the XGBoost algorithm model was 0.856(95% CI: 0.799-0.913), and the Hosmer-Lemeshow test showed that χ2=1.021, P=0.998. Conclusion:Logistic regression model and XGBoost algorithm model had similar prediction performance for MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS, and collateral circulation classification, number of thrombolysis, time from onset to recanalization, NIHSS score on admission, and age could be used as predictors.

Development of a mouse model of stellate ganglion block and subsequent effects on cerebral cortical blood flow / 中华麻醉学杂志

Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.

Lever positioning manipulation combined with pulsed electric field on the analgesic effect of patients with lumbar disc herniation and its influence on IL-1β and TNF-α / 中国骨伤

OBJECTIVE@#To observe the analgesic effect of lever positioning manipulation combined with pulsed electric field on patients with lumbar disc herniation and the influence on serum IL-1β and TNF-α.@*METHODS@#From January 2018 to March 2019, 58 patients with lumbar disc herniation were included in the study, which were randomly divided into observation group and control group by digital table method. Observation group of 29 cases, including 16 males and 13 females, aged (38.03±11.29) years old, were treated with lever positioning manipulation combined with pulsed electric field. The 29 cases in control group, including 17 males and 12 females, aged (38.21±9.16) years old, were treated with pulsed electric field. Both groups of patients were treated 3 times a week, once every other day, 3 times as a course of treatment. After 2 courses of treatment, the two groups of patients were scored before and after treatment by the numeric rating scales (NRS);at the same time, the serum levels of IL-1β and TNF-α were measured before and after treatment.@*RESULTS@#The NRS scores of observation group and control group were 4.21±1.76, 4.66±1.61 before treatment, and 1.28±0.84, 2.10±1.35 after treatment, respectively. The NRS scores of the observation group after treatment was significantly lower than that of the control group (@*CONCLUSION@#The lever positioning manipulation combined with pulsed electric field has a good analgesic effect on patients with lumbar disc herniation, and it has a significant impact on the patient's serum IL-1β and TNF-α concentration, which can be used as a clinical guide. However, the synergistic effect of lever positioning technique combined with pulsed electric field and guidelines for clinical treatment need further research.

Impact of low level viremia on the antiviral effect of human immunodeficiency virus/acquired immunodeficiency syndrome patients received anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the impact of low level viremia (LLV) on the prognosis of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients received anti-retroviral therapy (ART).Methods:From January to December 2015, the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital, Guangzhou Medical University (LLV group). Patients with viral load (VL) less than 50 copies/mL were matched at ratio of 1∶1 according to gender, age and the transmission route were included in the control group (suppression group). The LLV group was divided into three subgroups according to VL (LLV-1 subgroup was 50-200 copies/mL, LLV-2 subgroup was 201-400 copies/mL, and LLV-3 subgroup was 401-1 000 copies/mL). The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:One hundred and thirty-seven patients were enrolled in the LLV group, of whom 111 were males and 26 were females, with age of (39.5±13.5) years old. At the same time, 137 patients were included in the suppression group. There were 93 cases in LLV-1 subgroup, 25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup. There were no significant differences in the CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte counts ratios between LLV group and suppression group before ART (both P>0.05). During the three-year follow-up, the cumulative number of viral failures in LLV group (7.3%(10/137)) was significantly higher than that in the suppression group (1.5%(2/137)) ( χ2=5.578, P=0.018). Virological failure occurred in eight patients (8.6%) in the LLV-1 subgroup, two patients (8.0%) in the LLV-2 subgroup, and no patients in the LLV-3 subgroup. There was no statistical significance in the incidence of virological failure among all the subgroups ( P>0.05). At one, two, three years follow-up, the CD4 + T lymphocyte counts increased in both LLV group and suppression group without statistical differences (all P>0.05), and the CD4 + /CD8 + T lymphocyte counts ratios in each LLV group were lower than that in the suppression group ( Z=-3.183, -2.094 and -2.312, respectively, all P<0.05). At one, two, three years follow-up, There were no significant differences in CD4 + /CD8 + T lymphocyte counts ratios among the LLV-1, LLV-2 and LLV-3 subgroups (all P>0.05). Conclusion:HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function, which requires early relevant interventions.

Clinical effect of lever positioning manipulation for lumbar disc herniation and its influence on Cobb angle / 中国骨伤

OBJECTIVE@#To observe the clinical effect of lever positioning manipulation for the treatment of lumbar disc herniation and its effect on Cobb angle.@*METHODS@#From December 2017 to November 2018, 67 patients with lumbar disc herniation were included in the study. The patients were randomly divided into treatment group and control group by digital table method. There were 34 cases in the treatment group, including 20 males and 14 females, with an average age of (36.09±8.26) years old and a course of (13.79±15.50) months. Treatment group was treated with lever positioning manipulation. There were 33 cases in the control group, including 18 males and 15 females, with an average age of(36.48±7.81) years old and a course of (12.82±15.68) months. Control group was treated with lumbar slanting manipulation. Two groups were treated 3 times a week, once every other day, 6 times for a course of treatment, after 2 courses of treatment, the changes of Cobb angle before and after treatment were compared between two groups by imaging. The symptoms and signs were scored with reference to clinical evaluation standard;overall efficacy was evaluated with reference to "Diagnostic Efficacy Criteria of Traditional Chinese Medicine Syndrome" issued by the State Administration of Traditional Chinese Medicine for lumbar disc herniation.@*RESULTS@#One patient in each group dropped out. The symptom and sign scores of treatment group and control group before treatment were 18.56± 4.81, 18.61±3.72, while after treatment were 9.41±5.19, 13.55±3.68;treatment group was significantly lower than control group after treatment (@*CONCLUSION@#Both the lever positioning manipulation and the lumbar slanting manipulation methods are effective for the treatment of lumbar disc herniation, but clinical effect of lever positioning method on lumbar disc herniation is more significant, and the effect on Cobb angle is more obvious. It is worthy of promotion.

Effect of regulating menstruation and promoting pregnancy acupuncture therapy on negative emotion in patients with premature ovarian insufficiency / 中国针灸

OBJECTIVE@#To observe the influence of regulating menstruation and promoting pregnancy acupuncture therapy on negative emotions in patients with premature ovarian insufficiency (POI).@*METHODS@#A total of 60 patients with POI were randomly divided into an acupuncture group and a western medication group, 30 cases in each group. The acupuncture group was treated with regulating menstruation and promoting pregnancy acupuncture therapy at Baihui (GV 20), Shenting (GV 24), Guanyuan (CV 4), Sanyinjiao (SP 6), Shenshu (BL 23), Ciliao (BL 32), etc. once a day, 5 times a week for 3 months. The western medication group was treated by oral administration of climen. The drug was given 1 tablet a day for 21 days and was stopped for 1 week as a course. The treatment was required 3 consecutive courses. The self-rating anxiety scale (SAS) score, modified Kupperman index (KI) score, agitated and depressive symptom scores in KI and serum level of follicle stimulating hormone (FSH) before and after treatment were compared between the two groups.@*RESULTS@#After treatment, the SAS scores, KI scores and serum levels of FSH in the two groups and the scores of agitated and depressive symptom in the acupuncture group were lower than those before treatment (@*CONCLUSION@#Regulating menstruation and promoting pregnancy acupuncture therapy can effectively improve the negative emotions of patients with POI and reduce serum level of FSH .

Potential epitopes and mutation characteristics of 2019 novel coronavirus spike protein / 中华传染病杂志

Objective:To predict the epitopes of the spike protein of 2019 novel coronavirus (2019-nCoV) and to analyze the mutation characteristics of this protein.Methods:The gene sequences of 2019-nCoV was downloaded from GenBank and Global Initiative on Sharing All Influenza Data database (as of March 4, 2020). ClustalW, MEGA 7.0, Immune Epitope Database and other software were used for predicting potential B lymphocyte and T lymphocyte epitopes of spike protein, and then mutations were compared in epitope and non-epitope regions. Statistical analysis was performed with chi-square test.Results:There were 130 potential epitopes, including 25 linear B lymphocyte epitopes, 18 non-linear B lymphocyte epitopes, 71 human leukocyte antigen (HLA) class-Ⅰ restricted T lymphocyte epitopes, and 16 HLA class-Ⅱ restricted T lymphocyte epitopes in spike protein. S 404-426displayed the higher antigenicity-score, and its population coverage was 73.4% in China. Compared with the spike protein before January 31, the mutation frequencies of spike protein were increased both in non-epitope (15.4% vs 21.7%) and epitope regions (6.2% vs 8.7%) after January 31, but the differences were not statistically significant (both P>0.05). Conclusions:The study identifies several epitopes of 2019-nCoV spike protein, which provides a preliminary basis for the study of 2019-nCoV vaccine. Mutations in spike protein have an increasing trend which needs more attention and research in the future.

Study on the effect of chlorine disinfectants on the destruction of New coronavirus nucleic acid / 公共卫生与预防医学

Objective To observe the destructive effects of chlorine disinfectants on the nucleic acid of novel coronavirus, and to assess the feasibility of real-time fluorescent quantitative PCR technology for the evaluation of the disinfection effect of novel coronavirus. Methods A suspension quantitative inactivation test was used to observe the inactivation effects of different concentrations of chlorine containing disinfectants and different action times on the novel coronavirus. RT-PCR method was used to detect novel coronavirus nucleic acid for the disinfection effect evaluation. Results The chlorine disinfectants of 1 000 mg/L and 2 000 mg/L could destroy the nucleic acid of ew coronavirusafter application for over 30s. The chlorine disinfectant of 750 mg/L could destroy the nucleic acid of new coronavirusafter application for over 15min. Chlorine disinfectant of 500 mg/L could not completely destroy the nucleic acid of new coronavirusafter 30 min action. Conclusion The disinfection method stipulated in the national prevention and control plan using 1 000mg / L effective chlorine for the epidemic sites of new coronavirus for 30 minutes could completely destroy the nucleic acid of new coronavirus. The Real-time quantitative PCR can be used to evaluate the disinfection effect of new coronavirus.

Effect and Mechanism of Buyang Huanwu Tang on Atherosclerotic Plaque Based on Treg Cells / 中国实验方剂学杂志

Objective::To explore the effect and mechanisms of Buyang Huanwu Tang (BYHWT) on atherosclerotic plaque based on regulatory T cells (Treg) and inflammation. Method::Totally 50 ApoE knockout(ApoE-/-)mice aged 8 weeks were randomly divided into model group, low, medium, high-dose BYHWT groups, positive control group, and C57/BL mice were taken as control group. The model group and the BYHWT group were given high-fat diet for 12 weeks, while the control group was given normal diet. After successful modeling, BYHWT groups were given drugs (5, 10, 20 g·kg-1) through intragastric administration, the positive control group was given rapamycin (4 mg·kg-1), while the control group and the model group were given equal doses normal saline through intragastric administration for 4 weeks. Four weeks later, the mice were sacrificed. Manufactured paraffin sections were prepared for the aortic sinus of the heart. The plaque area was evaluated by hematoxylin and eosin (HE) staining, and the number of Treg cells in immunohistochemical staining plaque was detected. Blood was collected from eye canthus of mice, the expression of inflammatory factors in peripheral blood was detected by enzyme-linked immunosorbent assay (ELISA), and the forkhead box P3 (Foxp3) gene expression in peripheral blood was detected by Real-time fluorescent quantitative polymerase chain reaction (PCR). Result::Compared with the control group, the area of atherosclerotic plaques in the model group was significantly increased (P<0.01), the contents of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased (P<0.05), and transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were significantly decreased (P<0.05), and the peripheral blood Fxop3 mRNA expression was decreased (P<0.05). Compared with the model group, the plaque areas in middle-dose and high-dose BYHWT groups were significantly reduced(P<0.05), the peripheral blood TNF-α and IL-6 contents were decreased (P<0.01), the TGF-β and IL-10 expressions were increased in the high-dose group (P<0.05, P<0.01), the number of Treg cells in the plaque was increased in the high-dose group (P<0.01), and the peripheral blood Fxop3 mRNA expression was increased in each BYHWT group (P<0.01). Conclusion::BYHWT has an anti-atherosclerosis effect, which may be related to the increase of the number of Treg cells and thereby inhibiting the inflammatory response in vivo.

Erratum: Author correction to 'Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication' Acta Pharmaceutica Sinica B 9 (2019) 769-781

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Progress on in situ cell transdifferentiation in central nervous system / 生理学报

Central nervous system injury leads to irreversible neuronal loss and glial scar formation, which ultimately results in persistent neurological dysfunction. Regenerative medicine suggests that replenishing missing neurons may be an ideal approach to repair the damage. Recent researches showed that many mature cells could be transdifferentiated into functional neurons by reprogramming. Therefore, reprogramming endogenous glia in situ to produce functional neurons shows great potential and unique advantage for repairing neuronal damage and treating neurodegenerative diseases. The present review summarized the current research progress on in situ transdifferentiation in the central nervous system, focusing on the cell types, characteristics and research progress of glial cells that could be transdifferentiated in situ, in order to provide theoretical basis for the development of new therapeutic strategies of neuronal injury and further clinical application.

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

Clinical association between pre-treatment levels of plasma fibrinogen and bone metastatic burden in newly diagnosed prostate cancer patients / 中华医学杂志(英文版)

BACKGROUND@#Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients.@*METHODS@#A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression.@*RESULTS@#Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P 7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001).@*CONCLUSIONS@#Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.

Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity

PURPOSE: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. METHODS: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. RESULTS: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. CONCLUSIONS: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591550

Liraglutide prevents high glucose-induced adhesion of endothelial cells to monocyte by targeting IKK/NF-κB / 中国医师杂志

Objective To investigate the inhibition effect of liraglutide (lira) on high glucose-induced adhesion of endothelial cells to monocyte.Methods Human umbilical vascular endothelial cells (HUVECs) induced by high glucose (20 mmol/L) were incubated with different concentrations of liraglutide (0,0.3,3,30 nmol/L) for different time.THP-1 cells were pre-labeled with Calcein-AM and then incubated with HUVECs for 1 h,M199 medium were used for washing the nonadherent cells for 3 times,and the adhesion of HUVECs to THP-1 cells were measured by Fluorence microplate reader;real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were employed to detect the mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1),respectively.Western blot was used to measure the content of IκBα,p-IκBα and the distribution of p65 in plasma and nuclear.GST-IκBα was introduced as substrate to test the activity of IκB-kinase (IKK).Results The adhesion of HUVECs to THP-1 (P ＜ 0.01),the mRNA and protein expression of VCAM-1 and ICAM-1 (P ＜ 0.05,P ＜ 0.01),the phosphorylation of κBα (P ＜ 0.05,P ＜ 0.01),the translocation of p65 subunit from plasma to nuclear and the activity of IKK (P ＜ 0.01) in HUVECs were all elevated by stimulation with 20 mmol/L glucose,and the content of IκBα was decreased accordingly (P ＜0.01).Pre-incubation with lira could reverse the above effect of high concentration of glucose.Conclusions Lira could reduce VCAM-1 and ICAM-1 expression through IKK/NF-κB pathways in 20 mmol/L glucose-induced HUVECs,which finally suppress THP-1-HUVECs adhesion.

Non-surgical management of uterine myoma / 中国实用妇科与产科杂志

Uterine fibroids are benign diseases with high incidence and unknown pathogenesis.Currently,fibroid excavation or hysterectomy is the most commonly used treatment,but for women who require conservative treatment or with fertility requirements,there is still no optimal treatment option.At present,GnRH agonists/antagonists,selective progesterone receptor antagonists,levonorgestrel sustained release,uterine artery embolization,high-intensity focused ultrasound and other non-traditional surgical treatments provide new treatment options for conservative treatment of uterine fibroids from different angles.

Early complications after robot-assisted laparoscopic radical cystectomy and their risk factors / 中南大学学报(医学版)

To identify risk factors for early complications in patients after robot-assisted laparoscopic radical cystectomy (RARC) and a standardized reporting model to predict complications precisely and recommend reasonable prophylaxis.
 Methods: A total of 90 patients with bladder cancer, who underwent RARC in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2016 to January 2018, were enrolled for this study. Their clinical information, preoperative examination and follow-up data within 90 d after RARC were collected. Univariable and multivariable logistic regressions were performed to identify risk factors for early complications after RARC.
 Results: The overall incidence of complications within 90 d after RARC was 48.9% (44/90), including 9 cases of Clavien grade 1, 17 cases of Clavien grade 2, 4 cases of Clavien grade 3, 12 cases of Clavien grade 4, and 2 cases of Clavien grade 5. Acute renal injury (22.2%), intestinal obstruction (16.7%), urinary tract infection (14.4%) and lymphatic leakage (10.0%) were the most common complications within 90 d after the operation. Two patients (2.2%) died within 90 d after the operation. Preoperative BMI (OR=1.16, 95% CI 1.02 to 1.32), postoperative instant (≤30 min) serum creatinine (OR=1.02, 95% CI 1.00 to 1.03), and pT stage (OR=1.67, 95% CI 1.05 to 2.68) were the risk factors for early complications after RARC. 
 Conclusion: The incidence of early complications after RARC is high. Preoperative hemodialysis, correction of anemia, intraoperative protection of renal function, and early recovery after surgery are helpful to prevent early complications after RARC.

Clinical association between pre-treatment levels of plasma fibrinogen and bone metastatic burden in newly diagnosed prostate cancer patients / 中华医学杂志(英文版)

Background@#Due to the different treatments for low-volume metastatic prostate cancer (PCa) as well as high-volume ones, evaluation of bone metastatic status is clinically significant. In this study, we evaluated the correlation between pre-treatment plasma fibrinogen and the burden of bone metastasis in newly diagnosed PCa patients.@*Methods@#A single-center retrospective analysis, focusing on prostate biopsies of newly diagnosed PCa patients, was performed. A total of 261 patients were enrolled in this study in a 4-year period. All subjects were submitted to single-photon emission computerized tomography-computed tomography to confirm the status of bone metastasis and, if present, the number of metastatic lesions would then be calculated. Clinical information such as age, prostate-specific antigen (PSA), fibrinogen, clinical T stage, and Gleason score were collected. Patients were divided into three groups: (i) a non-metastatic group, (ii) a high volume disease (HVD) group (>3 metastases with at least one lesion outside the spine), and (iii) a low volume disease (LVD) group (metastatic patients excluding HVD ones). The main statistical methods included non-parametric Mann-Whitney test, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression.@*Results@#Fibrinogen positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and number of metastatic lesions (r = 0.296, P < 0.001). Compared with the non-metastatic and LVD groups, the HVD group showed the highest PSA (104.98 ng/mL, median) and fibrinogen levels (3.39 g/L, median), as well as the largest proportion of Gleason score >7 (86.8%). Both univariate (odds ratio [OR] = 2.16, 95% confidential interval [CI]: 1.536-3.038, P < 0.001) and multivariate (OR = 1.726, 95% CI: 1.206-2.472, P = 0.003) logistic regressions showed that fibrinogen was independently associated with HVD. The ROC curve suggested that fibrinogen acts as a predictor of HVD patients, yielding a cut-off of 3.08 g/L, with a sensitivity of 0.684 and a specificity of 0.760 (area under the curve = 0.739, 95% CI: 0.644-0.833, P < 0.001).@*Conclusions@#Pre-treatment plasma fibrinogen is positively associated with bone metastatic burden in PCa patients. Our results indicate that fibrinogen might be a potential predictor of HVD.