Revealing the mechanisms of Arisaema cum Bile on allergic asthma with systematic pharmacology approach-experimental validation.

Arisaema cum Bile (Dan Nanxing in Chinese, DNX) have been employed to treat allergic asthma. However, the active components and its mechanisms remain unknown. Therefore, the systematic pharmacology approach-experimental validation was performed in this study. Each 5, 6, and 10 compounds of DNX were obtained by HPLC analysis, TCMSP, and literature report, respectively. A total of 379 targets on all these compounds were acquired from Swiss Target Prediction, and 1973 targets on allergic asthma were predicated. The KEGG enrichment analysis was performed. Furthermore, a rat model of allergic asthma was established and DNX (450 mg/kg, p.o.) was given for 2 weeks. DNX treatment prevented OVA-induced pathological changes in lung cell of irregular arrange and necrotic bronchial epithelial. It also decreased inflammatory cytokines IL-4, IL-5, and IL-13 of serum and BALF, and increased IL-12 and IFN-γ. The main MAPK signaling pathway predicted by KEGG enrichment was verified, as indicated by the decreased protein expression of JNK (p < 0.05 & p < 0.01), ERK (p < 0.05), and p38 MAPK (p < 0.01) in lung tissue. These findings indicated that DNX attenuated OVA-induced allergic asthma mainly by decreasing the MAPK signaling pathway.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Surgical treatment for male prolactinoma: A retrospective study of 184 cases.

A total of 184 cases of surgically treated male prolactinoma were analyzed retrospectively to summarize the outcome of this surgical intervention. We analyzed the general characteristics, clinical manifestations, hormone levels, imaging features, preoperative treatments, surgical outcomes, pathology results, and follow-up records for all included patients. The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. Pituitary adenomas grew in a parasellar pattern with visual deficits occurring 40.7% of the time. After surgical therapy, 88.6% of patients achieved symptom relief, and 98.4% experienced an immediate postoperative decline in prolactin level. Fifty-seven patients (31.0%) achieved initial remission, and 26 patients (45.6%) experienced recurrence. Hence, our results suggest that in male prolactinoma characterized by a large pituitary diameter and high serum prolactin level, tumor size predicts the degree of gross resection. The prognostic predictors included preoperative tumor growth pattern and Ki-67 index.Citation: Yi-jun S, Mei-ting C, Wei L, Bing X, Yong Y, Ming F, Ren-zhi W. (2016) Surgical treatment for male prolactinoma: a retrospective study of 184 cases.

The suppression of epileptiform discharges in cultured hippocampal neurons is regulated via alterations in full-length tropomyosin-related kinase type B receptors signalling activity.

Epilepsy is a common neurological disease. Understanding the mechanisms of epileptogenesis at the cellular and molecular levels may provide novel targets for preventing this disorder. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase type B (TrkB) are believed to be critical for epileptogenesis. Previous studies have revealed possible changes in the expression of full-length TrkB receptors (TrkB.FL) and truncated TrkB receptors (TrkB.T) in neurodegenerative disorders. In this study, we investigated alterations in TrkB receptor expression and TrkB signalling activity in a rat hippocampal neuronal model of spontaneous recurrent epileptiform discharges (SREDs) and the effects on the epileptiform discharges. To induce epileptiform discharges, we established a model with Mg(2+) -free treatment. We found a dramatic upregulation of TrkB.T and a decrease in TrkB.FL in the SREDs model. Calpain contributed to the downregulation of TrkB.FL. The upregulation of TrkB.T required transcription and translation activity. Furthermore, BDNF induced the activation of TrkB.FL signalling. However, TrkB.FL signalling was inhibited in the SREDs model. Although calpain inhibitors prevented a decrease in TrkB.FL, they did not restrain the downregulation of TrkB.FL signalling activity in the model. However, a SREDs model with a translation inhibitor prevented the increase in TrkB.T and re-activated TrkB.FL signalling activity. Finally, we used electrophysiology to observe that a downregulation of TrkB.T could relieve the representative epileptiform discharges in the model. These results, taken together, demonstrate that alterations in TrkB.FL signalling may be regulated via TrkB.T receptors. Upregulation of TrkB.FL signalling suppresses epileptiform discharges in the SREDs model.

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis.

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10⁻¹°, 3.03 × 10⁻¹¹, 3.77 × 10⁻¹¹ and 4.65×10⁻¹¹ mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

BCL2A1 is a potential biomarker for postoperative seizure control in patients with low-grade gliomas.

AIMS: To identify molecular genetic factors that influence preoperative seizure occurrence and postoperative seizure control in patients with low-grade gliomas (LGGs). METHODS: Fifty-four WHO grade II astrocytomas were used for microarray analysis under strict inclusion criteria. The primary endpoint was seizure control at 12 months after surgery. Biological processes were investigated by gene ontology (GO) analysis. Quantitative RT-PCR and immunohistochemistry were used to validate key genes. RESULTS: Differentially expressed genes correlated with seizure occurrence failed to significantly distinguish patients with and without a history of seizures. With respect to postoperative seizure control, a transcript profile of 92 genes was identified, which successfully separated patients with good and poor seizure prognosis. GO analysis revealed that the most striking overrepresentation of genes was found in a category of anti-apoptotic genes and their regulation. Increased expression was also observed for genes involved in immune and inflammatory responses. BCL2A1 was proven to be a novel marker associated with seizure prognosis. CONCLUSION: Increased anti-apoptotic activity of tumor cells appears to contribute to seizure recurrence after surgery in patients with LGGs. These findings provide insights that may lead to the development of effective treatment strategies for prolonging the survival of patients with LGG in the future.

Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study.

Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.

Temporal lobe epilepsy induces differential expression of hippocampal miRNAs including let-7e and miR-23a/b.

To understand the role of miRNAs in the molecular mechanisms of temporal lobe epilepsy (TLE), we investigated the changes in microRNA (miRNA) expression profiles of chronic TLE rat models. MiRNAs microarray analysis results showed that 125 miRNAs were detected in the hippocampus of lithium-pilocarpine-induced TLE rats and normal rats. Compared with normal rats (control group), 23 of the 125 miRNAs were expressed differentially in TLE rats including 5 down-regulated miRNAs (let-7 e included) and 18 up-regulated miRNAs (miR-23 a/b included). Furthermore, let-7 e and miR-23 a/b analysis in rat hippocampus were performed by real-time quantitative polymerase chain reaction at 0 h, 1h, 6h, 12h, 24h, 2 days, 7 days,10 days, 30 days,50 days after induction of status epilepticus (SE). let-7 e was detected down-regulated expression at 0 h, 1h, 6h, 2 days, 7 days, 50 days after SE and up-regulated expression at 12h, 24h, 10 days, 30 days after SE, which was significantly up-regulated expression at 24h after SE (10.49 folds, P<0.01). miR-23 a/b was detected down-regulated at 0 h, 1h, 6h, 12h, 2 days, 7 days, 10 days, 30 days after SE and significantly up-regulated at 24h (4.49 folds P<0.01), 50 d (2.4 folds, P<0.01) after SE. TLE alters the expression levels of a subset of miRNAs in the hippocampus and these deregulated miRNAs may be involved in the pathogenesis of epilepsy directly or indirectly. Also the temporal change of the let-7 e and miR-23 a/b expression in the epileptogenesis indicated their underlying functions on TLE.

[Predictors of maternal and fetal outcome in systemic lupus erythematosus: a retrospective study of 94 cases].

OBJECTIVE: To evaluate the predictors of maternal and fetal outcome of pregnancy for systemic lupus erythematosus (SLE) patients. METHODS: Ninety-four patients with 96 pregnancies which were evaluated retrospectively from Jan 1990 to Jan 2008 in Peking Union Medical College Hospital were divided into two groups: disease stable during pregnancy (group A) and lupus flares during pregnancy (group B). Statistical analysis was performed by chi(2) or Fisher exact test and Student's t-test. A binary logistic regression model was used to evaluate the predictors of maternal and fetal outcome. RESULTS: There were 36 pregnancies with stable lupus disease (group A) and 60 pregnancies with lupus flares (group B). Of the 96 pregnancies, 18 resulted in therapeutic abortion and 7 in fetal loss, 71 resulted in a live birth,3 in neonatal death. The rates of preterm delivery, small gestational age (SGA) and neonatal asphyxia in group B were higher than those in group A (P < 0.05). By binary logistic regression analysis, preeclampsia/eclampsia low serum platelet count and SLE flares were associated with poor fetal outcome (beta = 2.463, 2.228, 2.769 respectively, P < 0.05). There were 56 pregnancies with stable lupus disease at the conception with 22 (39.3%) occurred lupus flares during pregnancies. Twenty-four preeclampsia and 2 eclampsia were seen in all the pregnancies. Fifty-two pregnancies were complicated with lupus nephritis, and 25 pregnancies (48.1%, 25/52) of which were disease stable at the conception, and among 22 pregnancies with disease stable over one year, twelve of which occurred lupus nephritis flares. Three pregnancies which have disease activity within one year before pregnancy all occurred lupus nephritis flares. There were four maternal death which all occurred at the postpartum. By binary logistic regression analysis, lupus nephritis flares were associated with preeclampsia/eclampsia (beta = 2.658, P < 0.05), and proteinuria at the conception before delivery were significantly associated with SLE flares (beta = 3.263, P < 0.05). CONCLUSION: An increase of fetal loss, preterm delivery, SGA and neonatal asphyxia was seen in patients with lupus flares during pregnancy compared with those with stable disease. About 1/3 lupus activity may increase after pregnancy. Preeclampsia and eclampsia were increased when there were lupus nephritis flares.

[Effect of combined continued hormone replacement therapy on knee osteoarthritis symptom of postmenopausal women].

OBJECTIVE: To study the effect of combined continued estrogen and progestin replacement therapy on knee osteoarthritis (OA) symptoms of postmenopausal women. METHODS: Sixty-four postmenopausal women with radiological knee OA and symptoms aged 45-75 were divided into treatment group and control group. They were given estradiol velerate (E2V) 1.0 mg/d and medroxyprogestetone acetate (MPA) 2 mg/d (treatment group) or placebo (control group) for 6 months. Calcium 400 mg/d were given to all cases. Then 0-100 mm visual analon scale (VAS) was used to evaluate the severity of knee pain at baseline and after 1, 3, 6 month of treatment. RESULTS: Significant differences on pain at night and tenderness around knee were seen in the treatment group compared with the control group after 1 months of treatment (P = 0.036 and 0.035, respectively). The improvement of pain at night, during walk and morning stiffness between the two groups showed significant difference after 6 months (P = 0.026, 0.027, and 0.011, respectively). CONCLUSION: Combined estrogen and progestin replacement therapy can relieve the knee OA symptoms of postmenopausal women.

[Prevalence and related factors of urinary incontinence in postmenopausal women].

OBJECTIVE: To investigate the prevalence of urinary tract atrophy and related factors to urinary incontinence in postmenopausal women in the urban area of Beijing. METHODS: Subjects were selected from 4 central districts in Beijing with a multiple-stage randomly sampling procedure. A total of 1,257 postmenopausal women aged 60 years or over received interviews on lower urinary tract symptoms and physical examinations. The prevalences of different urinary tract symptoms were calculated. Logistic regression analysis was used to find the related factors of urinary incontinence. RESULTS: The prevalence of urinary incontinence of postmenopausal women was 61.0%. Stress urinary incontinence had the highest prevalence (64.5%). While the prevalence of nocturia was 66.8%. Logistic regression analysis indicated that stress urinary incontinence in postmenopausal women was associated with the following factors: obesity, long education years, long-time standing, and low ability of bending or squatting. High grip strength might reduce the risk of urinary stress incontinence. Urge incontinence was associated with obesity, while higher education and high grip strength might reduce the risk of urge incontinence. CONCLUSIONS: Incontinence is very common in postmenopausal women. The prevalence in this study is even higher than that in other reports. Obesity and muscle strength are related to the prevalence of urinary incontinence in subjects over 60 in Beijing.

[The effect of estrogen and progestin on the expression of matrix metalloproteinases, tissue inhibitor of metalloproteinase and interleukin-1beta mRNA in synovia of OA rabbit model].

OBJECTIVE: To observe the effect of different dose of estrogen or estrogen plus progestin on the mRNA expression of MMP-1, MMP-3, TIMP-1 and IL-1beta in synovia of female New Zealand White rabbit OA model. METHODS: Sixty-five female New Zealand White rabbits (3 kg +/-, 6 months old) were used in this study. Right knees of all the rabbits were immobilized for 5 weeks to get OA model. Then 5 rabbits were killed by overdose of anesthesia to guarantee the model. Sixty OA rabbits were randomly divided into 6 groups (A, B, C, D, E, F) with 10 each. Group A approximately E were ovariectomized and group F were sham ovariectomized. The rabbits were feed by estradiol valerate (E(2)V) everyday as follows. Group A: E(2)V 1.8 mg/d, group B: E(2)V 3.6 mg/d, group C: E(2)V 7.2 mg/d, group D: E(2)V 3.6 mg/d + MPA 3.6 mg/d, group E was the untreated control group, group F was the untreated sham control group. Five rabbits of each group were killed respectively in 8 and 16 weeks and synovia of the right knee were obtained on all knees. Reverse transcription- polymerase chain reaction were used to detect the mRNA expression of MMP-1, MMP-3, TIMP-1 and IL-1beta in the OA synovia to determine the effect of estrogen and progestin. RESULTS: RT-PCR shows an increase expression of mRNA of MMP-1, MMP-3 and IL-1beta in OA synovia tissue in ovariectomized rabbits. Estrogen supplement could decrease the expression, an enhancement effect could be observed with progestin. Low dose estrogen could decrease the ratio of MMP-1/TIMP-1 and MMP-3/TIMP-1, which could even be decreased by progestin. High dose estrogen could slightly increase the ratio, but still lower than the untreatment control group. CONCLUSION: Our study suggests that certain dose estrogen and perhaps appropriate estrogen and progestin ratio are much important to the normal effect of articular cartilage. Estrogen deficiency or much high estrogen level could both show a damage effect on articular cartilage.