Classical swine fever virus non-structural protein 4A recruits dihydroorotate dehydrogenase to facilitate viral replication.

Mitochondria are energy producers in cells, which can affect viral replication by regulating the host innate immune signaling pathways, and the changes in their biological functions are inextricably linked the viral life cycle. In this study, we screened a library of 382 mitochondria-targeted compounds and identified the antiviral inhibitors of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo synthesis pathway of pyrimidine ribonucleotides, against classical swine fever virus (CSFV). Our data showed that the inhibitors interfered with viral RNA synthesis in a dose-dependent manner, with half-maximal effective concentrations (EC50) ranging from 0.975 to 26.635 nM. Remarkably, DHODH inhibitors obstructed CSFV replication by enhancing the innate immune response including the TBK1-IRF3-STAT1 and NF-κB signaling pathways. Furthermore, the data from a series of compound addition and supplementation trials indicated that DHODH inhibitors also inhibited CSFV replication by blocking the de novo pyrimidine synthesis. Remarkably, DHODH knockdown demonstrated that it was essential for CSFV replication. Mechanistically, confocal microscopy and immunoprecipitation assays showed that the non-structural protein 4A (NS4A) recruited and interacted with DHODH in the perinuclear. Notably, NS4A enhanced the DHODH activity and promoted the generation of UMP for efficient viral replication. Structurally, the amino acids 65-229 of DHODH and the amino acids 25-40 of NS4A were pivotal for this interaction. Taken together, our findings highlight the critical role of DHODH in the CSFV life cycle and offer a potential antiviral target for the development of novel therapeutics against CSF. IMPORTANCE: Classical swine fever remains one of the most economically important viral diseases of domestic pigs and wild boar worldwide. dihydroorotate dehydrogenase (DHODH) inhibitors have been shown to suppress the replication of several viruses in vitro and in vivo, but the effects on Pestivirus remain unknown. In this study, three specific DHODH inhibitors, including DHODH-IN-16, BAY-2402234, and Brequinar were found to strongly suppress classical swine fever virus (CSFV) replication. These inhibitors target the host DHODH, depleting the pyrimidine nucleotide pool to exert their antiviral effects. Intriguingly, we observed that the non-structural protein 4A of CSFV induced DHODH to accumulate around the nucleus in conjunction with mitochondria. Moreover, NS4A exhibited a strong interaction with DHODH, enhancing its activity to promote efficient CSFV replication. In conclusion, our findings enhance the understanding of the pyrimidine synthesis in CSFV infection and expand the novel functions of CSFV NS4A in viral replication, providing a reference for further exploration of antiviral targets against CSFV.

A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml / 亚洲男科学杂志(英文版)

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml

[Vasovagal syncope or postural orthostatic tachycardia syndrome in children with neurological symptoms at disease onset: a clinical analysis of 88 cases].

OBJECTIVE: To study the clinical features of vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children with neurological symptoms at disease onset. METHODS: A retrospective analysis was performed on the medical data of 88 children with the initial symptoms of the nervous system, such as transient loss of consciousness, dizziness, headache, and convulsion, who were finally diagnosed with VVS or POTS. RESULTS: Of the 88 children, there were 35 boys (40%) and 53 girls (60%), with an age of 4-15 years. The peak age of onset was between 10 and 13 years. All the children had the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. Nervous system diseases were excluded by electroencephalography, cerebrospinal fluid examination, and cranial MRI. Of the 88 children, 53 (60%) were confirmed with VVS, and 35 (40%) with POTS, according to the results of head-up tilt test (HUTT). Five children with the initial symptom of transient loss of consciousness were misdiagnosed with epilepsy. Predisposing factors were determined for 59 children (67%), and prolonged standing was the most common factor, followed by change in body position and strenuous exercise. Premonitory symptoms were observed in 66 children (75%), among which chest discomfort was the most common symptom, followed by gastrointestinal symptoms (nausea, vomiting, and abdominal pain) and pale complexion. All 88 children received health education and exercise for autonomic nerve function, among whom 53 children with VVS were given oral rehydration salts and 35 children with POTS were given oral rehydration salts and metoprolol. All 88 children were followed up for 18 months, and the response rates to the above treatment at 3, 6, 12, and 18 months of follow-up were 87%, 93%, 93%, and 90% respectively. CONCLUSIONS: In addition to nervous system diseases, functional cardiovascular diseases including VVS and POTS should be considered for children with the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. HUTT can be used to make a confirmed diagnosis, and the early treatment can achieve a good outcome.

Novel NtA and LG1 Mutations in Agrin in a Single Patient Causes Congenital Myasthenic Syndrome.

Congenital myasthenic syndrome (CMS) is a group of genetic disorders of neuromuscular transmission that is characterized by muscle weakness. A mutation in the gene encoding agrin (AGRN) is a rare cause of CMS, and only a few families or isolated cases have been reported. We reported a pediatric proband exhibiting muscle weakness in the trunk and limbs with skeletal malformation and intellectual disability and performed whole-exome sequencing (WES) of the proband parent-offspring trio. Results revealed a new compound heterozygous mutation in AGRN: c.125A>C (p.Glu42Ala) in the N-terminal agrin domain (NtA) and c.4516G>A (p.Ala1506Thr) in the laminin G1 domain (LG1). Bioinformatic analysis predicted the mutation as possibly pathogenic. The new compound heterozygous mutation in AGRN may disrupt agrin's known function of bridging laminin and α-dystroglycan and undermine the formation and maintenance of the neuromuscular junction (NMJ) via both muscular and neural agrin pathways. It may also induce secondary peripheral neuropathy and skeletal malformation.

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in children. / 儿童抗N-甲基-D-å¤©å†¬æ°¨é ¸å—ä½“è„‘ç‚Žçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To analyze the clinical characteristics and prognosis of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and to provide a basis for early clinical identification of this disease. METHODS: The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively. RESULTS: There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (P<0.05). After 3-39 months of follow-up, mRS score at 3 months after discharge was only 0.81±1.29, which was still improved compared with that at discharge, 76.2% cases (32/42) experienced complete or near-complete recovery (mRS score≤2), and 4.8% (2/42) cases relapsed. There was no mortality; the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis. The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were, the better the prognosis was. CONCLUSIONS: Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.

Clinicopathological characteristics of dysplastic teratomous neuroglia with anti-N-methyl-d-aspartate receptor encephalitis.

In this study, we investigated whether unique pathological characteristics exist in teratomas that can trigger autoimmune anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We compared a case of retroperitoneal teratoma associated with anti-NMDAR encephalitis and four control cases. The encephalitis-positive case showed that (i) more dysplastic neuroglia with higher Ki-67 labeling index values than the control cases, which met the diagnostic criteria of astrocytoma, (ii) the NMDAR subunit NR1 was expressed more abundantly in neuroglial tissue where many neuroglial cells co-expressed glial fibrillary acidic protein (GFAP) and NR1 and formed abnormally large cellular masses, (iii) intense NR1 expression occurs in squamous epithelium near neuroglial tissue and lymphocyte infiltration. This study showed that dysplastic neuroglial tissue resembling central nervous system tumors, which might promote autoimmunity, distinguished the case with NMDAR encephalitis from the controls. Additionally, abnormal expression of NR1 occurs in non-neural tissues and could be triggered by inflammation and participate in autoimmunity.

A rare case of pediatric moyamoya disease with reversible white matter lesions in a 3-year-old Chinese girl.

Moyamoya disease is a chronic cerebral vascular disease characterized by progressive occlusion of the cerebral arteries and resulting in the development of abnormal collateral circulation. We report a case of moyamoya disease in a 3-year-old Chinese girl with partly reversible white matter lesions. This case indicates that, in pediatric moyamoya disease, white matter lesions may be associated with cerebral ischemia, and they may be reversible after treatment.

Early-onset epileptic encephalopathy with de novo SCN8A mutation.

Early-onset epileptic encephalopathies (EOEEs) are clinically and genetically heterogeneous disorders characterized by intractable seizures and unremitting interictal paroxysmal epileptiform activity. Consequently, these syndromes impair neurodevelopment during the first year of life. Currently, the etiology of these disorders is largely unknown. In this study, Childhood-Onset Epilepsy Gene Panel Testing (containing 511 epilepsy-related genes) was performed in a parent-offspring trio. In this family, the son had refractory seizures, intellectual disability, and motor abnormalities, and he was diagnosed with EOEE. The boy later died from a sudden unexpected death in epilepsy (SUDEP) at the age of 26 months. In this case, we identified a de novo mutation (c.4423G > A; glycine [Gly]1475 arginine [Arg]) classified as heterozygous missense located in the inactivation gate section of the SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. This result strengthens the association between the SCN8A gene and EOEE, and more attention should be given to its high rate of SUDEP. Further studies to determine the pathogenic mechanisms of SCN8A mutations should be warranted at the inactivation gate section of this sodium channel in both neurons and cardiac muscles.

Histological subtype is a significant predictor for inguinal lymph node metastasis in patients with penile squamous cell carcinoma / 亚洲男科学杂志(英文版)

The present study aimed to investigate the relationship between histopathological subtype and the probability of inguinal lymph node metastasis (ILNM) in patients with penile squamous cell carcinoma (PSCC). The clinical records of 198 consecutive patients with PSCC were analyzed retrospectively. Primary lesions were reevaluated according to the 2016 World Health Organization (WHO) histopathological classification. We retrieved the clinicopathological factors from the medical records including age, clinical lymph node stage, pathological tumor stage, lymphatic invasion, and nerve invasion. Uni- and multivariate logistic regression analyses were used to explore the risk factors of ILNM. Multivariate analyses identified clinical lymph node stage (P = 0.000), pathological tumor stage (P = 0.016), histologic grade (P = 0.000), and risk group of histological subtypes (P = 0.029) as independent predictors for ILNM. Compared with the low-risk group of PSCC subtypes, the intermediate- (HR: 3.66, 95% CI: 1.30-10.37, P = 0.021) and high-risk groups (HR: 28.74, 95% CI: 2.37-348.54, P = 0.008) were significantly associated with ILNM. In conclusion, the histopathological subtype of the primary lesion is a significant predictor for ILNM in patients with PSCC.

Application of Lateral Three Layers Approach in Laparoscopic Pelvic Lymph Node Dissection / 中山大学学报(医学科学版)

[Objective] To investigate the safety and efficacy of lateral three layers approach in pelvic lymph node dissection.[Methods] From September 2016 to December 2017,12 patients 7 with bladder cancer,4 with prostate cancer and 1 with penile cancer underwent pelvic lymph node dissection were enrolled.The information of patients,complications,pathologic characteristics,and survival data were analysed.[Results] The patient average age was 60.5 (49～75) years.All operations were successful without conversion to open surgery.The average operation time was 52 (36～79) min,and the bleeding volume was 45 (25～110) mL.The postoperative complications within 30 days,Clavien Ⅰ-Ⅱ were 8 cases,Clavien Ⅲ-Ⅴ were 2 cases.The mean of lymph node dissection was 18.5,and lymph node positive percentage was 25.0％.[Conclusions] The lateral three layers approach in pelvic lymph node dissection was technically feasible.Our data has shown the recent oncological outcome is well.The outcome may need a long-term large sample study to further elaborate.

Alpha7 nicotinic acetylcholine receptor is required for amyloid pathology in brain endothelial cells induced by Glycoprotein 120, methamphetamine and nicotine.

One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aß) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of α7 nAChR in up-regulation of Aß induced by gp120, METH and NT. Aß release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of α7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of Aß, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and Aß in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that α7 nAChR may play an important role in neuropathology caused by gp120, METH and NT, which are the major pathogenic factors contributing to the pathogenesis of HAND.

MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures.

BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer's disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. RESULTS: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3. CONCLUSION: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures.

Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs.

The present study investigated whether atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators in human coronary artery endothelial cells (HCAECs). Several analysis methods, such as reverse transcription-quantitative polymerase chain reaction, western blot analysis and H2DCFDA incubation, were used in the present study. The data showed that atorvastatin decreased the visfatin-induced expression of interleukin (IL)-6 and IL-8 in HCAECs. In addition, atorvastatin inhibited the visfatin-induced expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HCAECs. In addition, the present study found that atorvastatin inhibited the visfatin-activated nuclear factor-κB (NF-κB) signal pathway by preventing extracellular signal-regulated kinase phosphorylation in HCAECs. Atorvastatin significantly inhibited visfatin-induced NF-κB activity via the upregulation of reactive oxygen species production. Atorvastatin, a visfatin antagonist (FK866) and an NF-κB inhibitor (BAY11-7082) decreased the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs. These results suggest that atorvastatin may inhibit the visfatin-induced upregulation of inflammatory mediators through blocking the NF-κB signal pathway. The findings of the present study provide a potential use for atorvastatin and visfatin in the pathogenesis of HCAEC dysfunction. This knowledge may contribute to the development of novel therapies for atherosclerosis.

Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation.

BACKGROUND: Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. Seizure-induced TLR4/MYD88 signaling plays a critical role in activating microglia and triggering neuron apoptosis. SAHA is a histone deacetylase inhibitor that regulates gene expression by increasing chromatin histone acetylation. In this study, we investigated the role of SAHA in TLR4/MYD88 signaling in a rat seizure model. RESULTS: Sprague-Dawley rats with kainic acid (KA)-induced seizures were treated with SAHA. The expression of TLR4, MYD88, NF-κB P65 and IL-1ß in hippocampus was detected at hour 2 and 6 and day 1, 2, and 3 post seizure. SAHA pretreatment increased seizure latency and decreased seizure scores. The expression levels of TLR4, MYD88, NF-κB and IL-1ß increased significantly in both activated microglia and apoptotic neurons after KA treatment. The effects were attenuated by SAHA. Chromatin immunoprecipitation assays indicated that the H3 histone acetylation levels significantly decreased while H3K9 levels significantly increased in the KA treatment group. The H3 and H3K9 acetylation levels returned to control levels after SAHA (50 mg/kg) pretreatment. There was a positive correlation between the expression of TLR4 and the acetylation levels of H3K9. CONCLUSIONS: Histone deacetylase inhibitor SAHA can suppress seizure-induced TLR4/MYD88 signaling and inhibit TLR4 gene expression through histone acetylation regulation. This suggests that SAHA may protect against seizure-induced brain damage.

Phloroglucinol combined with parecoxib for cystospasm after transurethral resection of the prostate / 中华男科学杂志

<p><b>Objective</b>To evaluate the effect and safety of phloroglucinol combined with parecoxib on cystospasm after transurethral resection of the prostate (TURP).</p><p><b>METHODS</b>We conducted a prospective randomized case-control study on 98 patients treated by TURP. After operation, the patients were randomly assigned to a treatment (n=50) and a control group (n=48), the former treated by intravenous injection of 80 mg phloroglucinol qd plus 40 mg parecoxib bid while the latter given 80 mg phloroglucinol only, both for 3 successive days. Then we recorded the frequency and duration of cystospasm, visual analogue scales (VAS), adverse reactions, post-operative bladder irrigation time, catheter-indwelling time, and hospital stay and compared them between the two groups of patients.</p><p><b>RESULTS</b>Compared with the controls, the patients in the treatment group showed a significantly lower frequency of cystospasm (［1.95±0.14］ vs ［0.70±0.65］ times, P<0.01), duration of cystospasm (［0.44±0.21］ vs ［0.12±0.14］ min, P<0.01), and VAS score (2.70±1.80 vs 1.90±1.30, P<0.01) at 48－72 hours after TURP, but no statistically significant differences were found between the control and treatment groups in the post-operative bladder irrigation time (［2.75±0.87］ vs ［2.64±0.83］ d, P>0.05), catheter-indwelling time (［3.52±0.32］ vs ［3.44±0.42］ d, P>0.05), and hospital stay (［5.23±0.81］ vs ［5.10±0.73］ d, P>0.05), and no obvious adverse reactions were observed in either of the two groups.</p><p><b>CONCLUSIONS</b>Phloroglucinol combined with parecoxib is more effective and safer than phloroglucinol alone in relieving postoperative cystospasm after TURP.</p>

Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy.

The pathogenesis of intractable epilepsy is not fully clear. In recent years, both animal and clinical trials have shown that the expression of ATP-binding cassette (ABC) transporters is increased in patients with intractable epilepsy; additionally, epileptic seizures can lead to an increase in the number of sites that express ABC transporters. These findings suggest that ABC transporters play an important role in the drug resistance mechanism of epilepsy. ABC transporters can perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs, thus causing resistance to antiepileptic drugs. Given the important role of ABC transporters in refractory epilepsy drug resistance, antiepileptic drugs that are not substrates of ABC transporters were used to obtain ABC transporter inhibitors with strong specificity, high safety, and few side effects, making them suitable for long-term use; therefore, these drugs can be used for future clinical treatment of intractable epilepsy.

Toxic effect of formaldehyde on mouse different brain regions / 生理学报

The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.

Safety and effectiveness of GreenLight 120-W laser photoselective vaporization of the prostate for benign prostatic hyperplasia: A meta-analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and effectiveness of GreenLight 120-W laser photoselective vaporization of the prostate (PVP) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We searched PubMed, Medline, Embase, Cochrane Library, Wanfang, CNKI, and VIP for randomized control trials and their references addressing 120-W PVP versus TURP in the treatment of BPH. Based on the inclusion and exclusion criteria, two reviewers independently accomplished the screening, quality assessment, and data extraction of the identified studies and performed meta-analyses using RevMan 5.2.</p><p><b>RESULTS</b>Totally, 6 randomized control trials were included in this analysis, involving 703 cases, 351 treated by PVP and 352 by TURP. Compared with TURP, PVP showed significantly decreased time of catheterization (by 32. 55 hours, 95% CI 15.3 -49.8, P < 0.01), hospital stay (by 1.85 days, 95% CI 1.2-2.5, P < 0.01), and intraoperative blood loss (by 15.6 g/L, 95% CI 10.0-21.2, P < 0.01), but increased time of operation (by 9.37 minutes, 95% CI 5. 1-13.6, P < 0.01). There was also a significant reduction in blood transfusion, TUR syndrome, and capsular perforation in the PVP group. At 12 months after surgery, no statistically significant differences were found between the two groups in the improvement of maximum urinary flow rate, IPSS, postvoid residual, and sexual function.</p><p><b>CONCLUSION</b>GreenLight 120-W laser PVP is a safe and effective procedure for the treatment of BPH, with similar effectiveness to TURP but less blood loss, shorter time of catheterization and hospital stay, and lower incidences of blood transfusion, TUR syndrome and capsular perforation.</p>

Puerarin Suppress Apoptosis of Human Osteoblasts via ERK Signaling Pathway.

Puerarin, the main isoflavone glycoside extracted from Radix Puerariae, is an isoflavone traditional Chinese herb. Previous studies have demonstrated that puerarin could regulate osteoblast proliferation and differentiation to promote bone formation. However, the effect of puerarin on the process of human osteoblasts (hOBs) apoptosis is still unclear. In this study, we detected the function of puerarin on serum-free-induced cell apoptosis using ELISA and TUNEL arrays and then found that the mortality of hOBs was significantly decreased after exposure to 10(-10)-10(-6) M puerarin and reached the maximal antiapoptotic effect at the concentration of 10(-8) M. In addition, compared with the control group, puerarin notably increased the Bcl-2 protein levels while it decreased the Bax protein levels in the hOBs in a dose-dependent way. 10(-7) M puerarin decreased the Bax/Bcl-2 ratio with a maximal decrease to 0.08. Moreover, puerarin activated ERK signaling pathways in hOBs, and the antiapoptotic effect induced by puerarin was abolished by incubation of ERK inhibitor PD98059. Similarly, the estrogen receptor antagonist ICI182780 also suppressed the inhibitory effect of puerarin on hOBs apoptosis. In conclusion, puerarin could prevent hOBs apoptosis via ERK signaling pathway, which might be effective in providing protection against bone loss and bone remolding associated with osteoporosis.