ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Function analysis of hospital mobile applications based on Kano model / 中华医院管理杂志

Objective To promote the building of the hospital mobile applications architecture in a scientific,user-centered,and needs-oriented way.Methods Function points from mobile applications were rounded up for classification and ranking by means of Kano model and double factor questionnaire survey,for the purpose of qualitative and quantitative analysis of 12 hospitals and identifying the core needs of patients.Statistical methods such as descriptive analysis were used to analyze the data.Results 16 function points of mobile applications were rounded up from 12 hospitals,finding that 12 of their 16 App functions were located in the upper half of the quartile graph,namely appointment and result inquiry.These 12 functions if well met will upgrade patient satisfaction.Conclusions High focus on mobile applications is imperative to upgrade hospital's intelligent medical services,improve the medical efficiency and satisfaction.

Antioxidant effect of a novel synthetic hydrogen sulfide releasing Danshensu derivative and its clinical implications / 中国药理学与毒理学杂志

Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu(DSS)and hydrogen sulfide(H2S)produce significant antioxidant effect in various systems. In this study,we synthesized SDSS,a new H2S-releasing compound derived from DSS,and studied its antioxidant effect in an H2O2-induced MC3T3-E1 osteoblastic cell injury model. We first characterized the H2S releasing property of SDSS in both in vivo and in vitro models. HPLC chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH,a well proved H2S sustained-release moiety, within several minutes in the rat plasma. Using an H2S selective fluorescent probe, we further confirmed that SDSS released H2S in MC3T3-E1 osteoblastic cells. Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H2O2-induced MC3T3-E1cell apoptosis. SDSS also reversed the arrest of cell differentiation caused by H2O2treatment. This was caused by the stimulatory effect of SDSS on bone sialo protein,runt-related transcription factor-2, collagen expression, alkaline phosphatase activity, and bone nodule formation. Further studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content,and the increased ROS production in H2O2treated cells. In addition, SDSS significantly attenuated H2O2-induced activation of p38-, ERK1/2-, and JNK-MAPKs. SDSS also stimulated phosphatidylinositol 3-kinase/Akt signaling pathway.Blockade of this pathway attenuated the cytoprotective effect of SDSS.We also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric damage. In conclusion, SDSS protects cells against H2O2-induced apoptosis by suppressing oxidative stress.

Kangle Decoction for erectile dysfunction with liver-qi stagnation and kidney deficiency / 中华男科学杂志

<p><b>Objective</b>To observe the clinical efficacy of Kangle Decoction in the treatment of erectile dysfunction (ED) with liver-qi stagnation and kidney deficiency.</p><p><b>METHODS</b>A total of 79 ED patients with liver-qi stagnation and kidney deficiency were randomly assigned to an experimental group (aged ［36.62±8.05］ yr and with a disease course of ［18.15±6.41］ mo) and a control group (aged ［37.44±8.10］ yr and with a disease course of ［17.51±6.79］ mo), the former treated orally with Kangle Decoction at 0.5 dose bid while the latter with Cialis at 10 mg qd alt, both for 8 weeks. Before treatment, after 4 and 8 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the scores of the patients in the International Index of Erectile Function-5 (IIEF-5), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Short-Form Psychological and Interpersonal Relationship Scales (SF-PAIRS), and compared the indexes between the two groups of patients.</p><p><b>RESULTS</b>The IIEF-5 score was dramatically increased in both the treatment and control groups after 4 weeks (13.40±2.42 and 16.00±2.68) and 8 weeks of medication (18.60±3.50 and 18.59±3.80) and at 4 weeks after drug withdrawal (17.00±3.05 and 13.95±2.61) as compared with the baseline (10.78±2.28 and 10.77±2.33) (P<0.05 ), even higher in the treatment than in the control group after drug withdrawal (P<0.05 ). The EDITS scores in the treatment and control groups were (28.88±3.31 and 28.90±3.31) after 4 weeks of intervention, (29.68±3.30 and 29.13±3.32) after 8 weeks of intervention, and (29.20±2.92 and 26.82±3.23) at 4 weeks after drug withdrawal, all significantly higher in the former than in the latter group after drug withdrawal (P<0.05 ). The sexual self-confidence score (SSCS), sexual spontaneity score (SSS), and sexual time-concern score (STCS) were all improved in the treatment and control groups after medication as compared with the baseline (P<0.05 ), even higher in the former than in the latter group after drug withdrawal (P<0.05 ).</p><p><b>CONCLUSIONS</b>Kangle Decoction has a definite efficacy in the treatment of ED with liver-qi stagnation and kidney deficiency, with few adverse reactions and long-term post-withdrawal effect, and therefore deserves a wide clinical application.</p>

Sertraline hydrochloride combined with four-spot caressing for primary premature ejaculation / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effectiveness of sertraline hydrochloride combined with four-spot caress in the treatment of primary premature ejaculation (PE).</p><p><b>METHODS</b>We randomly assigned 90 primary PE patients to three groups of equal number. The patients in group A (aged [28.1 ± 5.2] yr and with a disease course of [3.1 ± 1.9] yr) were treated with oral sertraline hydrochloride at 50 mg qd, those in B (aged [27.8 ± 4.1] yr and with a disease course of [3.2 ± 2.0] yr) by four-spot caressing (caressing the tongue, breasts, and vulva prior to intercourse), and those in C (aged [27.1 ± 4.7] yr and with a disease course of [3.1 ± 2.0] yr) by the combination of oral sertraline hydrochloride and four-spot caressing, all for 12 weeks. Before and after 4, 8, and 12 weeks of treatment, we obtained the intravaginal ejaculatory latency time (IELT) and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores and compared them among the three groups of patients.</p><p><b>RESULTS</b>The IELT was dramatically prolonged in groups A, B, and C after 4 weeks ([1.08 ± 0.29], [0.93 ± 0.28] and [1.21 ± 0.27] min), 8 weeks ([1.43 ± 0.30], [1.20 ± 0.33] and [1.72 ± 0.42] min) and 12 weeks of treatment ([2.12 ± 0.63], [1.90 ± 0.65] and [2.67 ± 0.82] min) as compared with the baseline ([0.63 ?0.14] , [0.60 ?0.14] and [0.62 ?0.11] min) (P < 0.05), even longer in group C than in A and B (P < 0.05). The CIPE-5 scores were markedly improved in groups A, B and C after 4 weeks ([15.17 ± 1.74], [14.57 ± 1.94] and [15.60 ± 1.63] min), 8 weeks ([17.13 ± 1.63], [16.37 ± 1.97] and [18.00 ± 1.05] min) and 12 weeks of intervention ([18.93 ± 1.57], [18.53 ± 1.67] and [20.00 ± 1.46] min ) as compared with the baseline ([12.57 ± 2.05], [13.20 ± 2.51] and [13.07 ± 2.01] min) (P < 0.05), even higher in group C than in A and B (P < 0.05).</p><p><b>CONCLUSION</b>Sertraline hydrochloride combined with four-spot caressing, with its definite efficacy and rare adverse reactions, deserves wide clinical application in the treatment of primary PE.</p>

Distribution, combination, and evolution of syndromic etiologies of erectile dysfunction / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory.</p><p><b>METHODS</b>Using the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients.</p><p><b>RESULTS</b>Through analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one.</p><p><b>CONCLUSION</b>In the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.</p>

Feasibility and efficiency of embolization of spinal dural arteriovenous fistula / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and efficiency of embolization of spinal dural arteriovenous fistula (SDAVF).</p><p><b>METHODS</b>From December 2010 to May 2012, there were 104 cases of SDAVF were treated, and 26 cases were selected to be treated with embolization. The inclusion criteria was as follows: (1) No anterior or posterior spinal artery originated from the fistula segment; (2) The segmental artery can be catheterized with guiding or micro catheter; (3) High flow in fistula; (4) Patient's situation was not suitable for surgery or general anesthesia. Among 26 cases, there were 22 male and 4 female patients, the average age was 55.9 years (ranged from 34 to 81 years). The locations of SDAVF were 10 cases in thoracic, 9 in lumbar and 7 in sacral segment. The main symptoms were progressive numbness and weakness in both lower extremities, most cases accompanied with difficulties in urination and defecation. The average history was 17.1 months (from 1 to 156 months). ONYX-18 liquid embolic agent or Glubran-2 surgical glue were used as embolic material. The patients not cured with embolization were treated with surgery in the following 1 - 2 weeks. Follow-up evaluation was done with MRI after 3 months and DSA after 6 months, besides physical examination.</p><p><b>RESULTS</b>Fifteen from 26 cases achieved immediate angiographic cure results: 14 in 20 cases which embolized with ONYX-18; only 1 in 6 cases with Glubran-2. Three in 10 cases of thoracic SDAVF and 12 in 16 cases of lumbar/sacral SDAVF were cured with embolization. Partially embolized cases were treated with surgical obliteration of drainage veins within 2 weeks. Cured patients experienced immediate improvement after embolization and kept getting better in the follow-up. All the patients had MRI follow-up after 3 months and DSA follow-up after 6 months. In 6 month's follow-up, MRI showed the edema and flow void signal in the spinal cord disappeared. DSA showed no fistula recurrence or remnant. There was no deterioration case in all of the embolized cases.</p><p><b>CONCLUSIONS</b>Particular SDAVF is suitable for embolization with ONYX-18. Most lesions located in lumbar and sacral segment are good indications for embolization.</p>

Effects of Jujingwan on nitric oxide and superoxide dismutase in seminal plasma of asthenospermia patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the possible action mechanism of Jujingwan on asthenospermia.</p><p><b>METHODS</b>Semen routine analyses and determination of nitric oxide (NO) concentration and superoxide dismutase (SOD) activity in seminal plasma were performed in 34 cases of asthenospermia. The changes of NO concentration and SOD activity before and after the treatment with Jujingwan were observed.</p><p><b>RESULTS</b>Compared with pre-treatment, there was no significant change in NO concentration, and the activity of SOD decreased significantly after the treatment ([95.97 +/- 20.75] microg/L vs [6.14 +/- 19.99] microg/L). There was negative correlation between NO concentration and SOD activity before the treatment (r = -0.246, P < 0.05).</p><p><b>CONCLUSION</b>Jujingwan can significantly improve sperm viability in patients with asthenospermia. However, the excellent effects of Jujingwan are not displayed in the changes of NO concentration and SOD activity.</p>

A report of 31 cases of asthenospermia treated by jujing granulation / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of Jujing granulation on asthenospermia.</p><p><b>METHODS</b>Thirty-six patients aged from 24 to 39 years with asthenospermia were received at our clinic of andrology from July 2004 to April 2005, and they were given Jujing granulation 120 ml twice a day for 3 months. The sperm parameters of the patients were analyzed by computer assisted sperm analysis system before and after Jujing granulation treatment.</p><p><b>RESULTS</b>Of the 31 patients who accomplished 3-month Jujing granulation therapy, only 3 remained unimproved in sperm parameters, while the other 28 were significantly improved in rapid sperm motility, forward sperm motility and total sperm motility, except in sperm density. Five of the patients' wives got pregnant and one had a child.</p><p><b>CONCLUSION</b>Oral Jujing granulation therapy is efficacious for asthenospermia.</p>