Selenium inhibits ferroptosis in hyperglycemic cerebral ischemia/reperfusion injury by stimulating the Hippo pathway.

Hyperglycemia can exacerbate cerebral ischemia/reperfusion (I/R) injury, and the mechanism involves oxidative stress, apoptosis, autophagy and mitochondrial function. Our previous research showed that selenium (Se) could alleviate this injury. The aim of this study was to examine how selenium alleviates hyperglycemia-mediated exacerbation of cerebral I/R injury by regulating ferroptosis. Middle cerebral artery occlusion (MCAO) and reperfusion models were established in rats under hyperglycemic conditions. An in vitro model of hyperglycemic cerebral I/R injury was created with oxygen-glucose deprivation and reoxygenation (OGD/R) and high glucose was employed. The results showed that hyperglycemia exacerbated cerebral I/R injury, and sodium selenite pretreatment decreased infarct volume, edema and neuronal damage in the cortical penumbra. Moreover, sodium selenite pretreatment increased the survival rate of HT22 cells under OGD/R and high glucose conditions. Pretreatment with sodium selenite reduced the hyperglycemia mediated enhancement of ferroptosis. Furthermore, we observed that pretreatment with sodium selenite increased YAP and TAZ levels in the cytoplasm while decreasing YAP and TAZ levels in the nucleus. The Hippo pathway inhibitor XMU-MP-1 eliminated the inhibitory effect of sodium selenite on ferroptosis. The findings suggest that pretreatment with sodium selenite can regulate ferroptosis by activating the Hippo pathway, and minimize hyperglycemia-mediated exacerbation of cerebral I/R injury.

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

Application of Internet+-based Tsinghua PINS Remote Tech to improve sacral neuromodulation programming procedure.

OBJECTIVE: To explore the feasibility and safety of the Tsinghua PINS Remote Tech to facilitate sacral neuromodulation programming procedure. METHOD: For 22 patients who had previously participated in the phase III clinical trial for treating overactive bladder with the Tsinghua PINS sacral neuromodulation system during several Hospital, PINS Remote Tech was applied to perform postoperative parameter adjustment in order to evaluate the safety and reliability of this new technique. Telephone surveys on Remote Tech-related questionnaires were also conducted. RESULTS: 17/22 patients underwent 26 parameter adjustments, average adjustment frequency was 1.53 times per person; the average adjustment time was 23.4 ± 5.1 min (15-32 min). The total effective rate of the Remote control was 14/17 (82.3%). 7/17 (41.1%) patients' symptoms recurrence due to not knowing how to handle patient controller, these patients were instructed on how to use it correctly through Remote Tech even without reprogramming it. Other 10 patients received reprogramming. There was no discomfort during and after parameter adjustment. The questionnaire survey showed that the remote technology saved patients' time and lowered financial costs, significantly improved patient satisfaction. All patients expressed their willingness to recommend it to other patients. CONCLUSION: The PINS Remote Tech can significantly reduce the financial cost and provide a remote reprogram control service that is as safe and reliable as outpatient program control.

[Progress in the treatment of premature ejaculation].

Premature ejaculation is a common disease in adult males, which may severely affect the mental health and distort the spousal relationship of the males. Treatment of premature ejaculation aims at increasing the intra-vaginal ejaculation latency time, enhancing the control of ejaculation and improving sexual satisfaction, and comprehensive treatment may help most to achieve these objectives. Though drug therapy remains an important option, there are many other effective strategies for the treatment of premature ejaculation, including psychotherapy, behavioral therapy, traditional Chinese medicine treatment, and surgery. Recently, various studies have demonstrated even better effects of a combination of the above strategies on premature ejaculation.

Hyperhomocysteinemia-induced autophagy and apoptosis with downregulation of hairy enhancer of split 1/5 in cortical neurons in mice.

It has been reported that hyperhomocysteinemia (HHcy) is associated with neurodegenerative and cardiovascular diseases. However, little is known about brain histomorphology, neuronal organelles, and hairy enhancer of split ( hes) expression under HHcy. In this study, non-HHcy and HHcy induced by high-methionine diet in apolipoprotein E-deficient (Apo E-/-) mice were comparatively investigated. The histomorphology, ultrastructure, autophagosomes, apoptosis, and expression of proteins, HES1, HES5 and P62, were designed to assess the effects of HHcy on brain. The results showed that compared to the non-HHcy mice, the HHcy group had an increase in autophagosomes, vacuolization in mitochondria, and neuron apoptosis; treatment with folate and vitamin B12 reduced the extent of these lesions. However, the elementary histomorphology, the numbers of cortical neurons, and Nissl bodies had no significant difference between the HHcy and the non-HHcy groups or the group treated with folate and vitamin B12. Immunohistochemistry and immunofluorescence demonstrated a decrease in HES1- or HES5-positive neurons in the HHcy group when compared to the non-HHcy groups, wild-type, and Apo E-/- controls, or the HHcy mice with folate and vitamin B12 supplement. Western blots showed that HHcy induced a decreased expression of HES1 and HES5, or P62, in which the expression of HES1 and P62 was elevated by treating with folate and vitamin B12 supplement. These results suggest that HHcy-enhanced brain damage is associated with increased autophagy and neuronal apoptosis in Apo E-/- mice, in which downregulation of hes1 and hes5 is involved.

Effects of Appropriate Prolonged Sacral Neuromodulation Testing in Improving Implantation Rate of a Permanent Implantable Pulse Generator in Patients with Refractory Lower Urinary Tract Dysfunctions in Mainland China.

BACKGROUND: Sacral neuromodulation (SNM) has become an effective method for treating lower urinary tract voiding dysfunction during the past 20 years. Because of the expensive cost, the number of implantable pulse generator (IPG) implantations per year in China is far lower than that in Western developed countries since 2012. This study was to summarize the effects of the appropriate prolonged SNM testing time in improving the implantation rate of a permanent IPG in patients with refractory lower urinary tract symptoms (LUTS) in mainland China. METHODS: From January 2013 to June 2016, 51 patients with refractory LUTS received SNM therapy. In this study, we compared the conversion rate 2 weeks after the Stage I test and final actual conversion rate. We also observed the complications (such as pain, infection, and electrode displacement) and effectiveness. We tried to improve an appropriate prolonged test time which was favorable for improving the SNM conversion rate while ensuring safety and effectiveness. RESULTS: Among 51 patients receiving SNM therapy, 19 patients (mean age 45.0 ± 16.9 years) had poor Stage I test results, and on an average, the electrode was removed 27.4 ± 9.6 days after the surgery. In one patient, the electrode was removed within 2 weeks; when the remaining 18 patients were questioned 2 weeks after testing, none of the patients wanted to terminate the test, and all the 18 patients desired to prolong the testing time to further observe the treatment effect. The remaining 32 patients (mean age 46.7 ± 15.3 years) received Stage II permanent implantation at 19.6 ± 10.4 days after the surgery. The overall Stage I-II conversion was 62.7% (32/51) in this study. Within 2 weeks after the surgery, only eight patients received Stage II permanent implantation, and the conversion rate was only 15.7% (8/51), which was much lower than the overall conversion rate of 62.7%. Nearly 84.4% (27/32) of the patients received Stage II implantation within 4 weeks. None of the patients had incision infections. In one patient, the entire system was removed 1 month after Stage II implantation due to pain in the implantation site. CONCLUSIONS: Appropriate extension of the Stage I testing time of an SNM-barbed electrode could significantly improve the Stage II permanent implantation rate in Chinese refractory LUTS patients; there were no wound infections, and the postoperative complication rate was low. This study recommended that Stage I period of SNM therapy should be 4 weeks according to safety and successful conversion rate.

Selenium suppresses glutamate-induced cell death and prevents mitochondrial morphological dynamic alterations in hippocampal HT22 neuronal cells.

BACKGROUND: Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage. RESULTS: We find that glutamate-induced cytotoxicity was associated with enhancement of superoxide production, activation of caspase-9 and -3, increases of mitochondrial fission marker and mitochondrial morphological changes. Selenium significantly resolved the glutamate-induced mitochondria structural damage, alleviated oxidative stress, decreased Apaf-1, caspases-9 and -3 contents, and altered the autophagy process as observed by a decline in the ratio of the autophagy markers LC3-I and LC3-II. CONCLUSION: These findings suggest that the protection of selenium against glutamate stimulated cell damage of HT22 cells is associated with amelioration of mitochondrial dynamic imbalance.

Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance.

AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance. METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the (13)C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ(2) tests. RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin-resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city. CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.

Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study.

AIM: To determine the resistance patterns of Helicobacter pylori (H. pylori) strains isolated from patients in Beijing and monitor the change of antibiotic resistance over time. METHODS: In this prospective, serial and cross-sectional study, H. pylori cultures were successfully obtained from 371 and 950 patients (never receiving eradication) during 2009-2010 and 2013-2014, respectively. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin was determined by Epsilometer test. RESULTS: The resistance rates of isolates obtained during 2009-2010 were 66.8%, 39.9%, 34.5%, 15.4%, 6.7%, and 4.9% to metronidazole, clarithromycin, levofloxacin, rifampicin, amoxicillin and tetracycline, respectively; and the corresponding rates for isolates during 2013-2014 were 63.4%, 52.6%, 54.8%, 18.2%, 4.4% and 7.3%, respectively. The resistance rates to clarithromycin and levofloxacin were significantly increased after four years. In 2009-2010, 14.6% of H. pylori isolates were susceptible to all tested antibiotics, with mono (33.7%), double (28.3%), triple (16.7%), quadruple (6.2%), quintuple (0.3%) and sextuple resistance (0.3%) also being detected. In 2013-2014, 9.4% were susceptible to all tested antibiotics, and mono (27.6%), double (28.4%), triple (24.9%), quadruple (7.3%), quintuple (2.3%) and sextuple resistance (0.1%) was also observed. More multiple resistant H. pylori isolates were found during 2013-2014. Gender (to levofloxacin and metronidazole), age (to levofloxacin) and endoscopic findings (to clarithromycin) were independent factors influencing antibiotic resistance. CONCLUSION: H. pylori resistance to commonly used antibiotics in Beijing is high with increased multiple antibiotic resistance.

Successful isolation of Helicobacter pylori after prolonged incubation from a patient with failed eradication therapy.

Helicobacter pylori (H pylori), a gastric pathogen, is a major cause of chronic gastritis and peptic ulcer disease, and is an important risk factor for the development of gastric malignancies. Culture of the bacterium from gastric biopsy is essential for the determination of drug resistance of H pylori. However, the isolation rates of H pylori from infected individuals vary from 23.5% to 97% due to a number of factors such as biopsy preparation, cultural environment, medium and the method adopted. In the present case, we found that a prolonged incubation period of up to 19 d allowed successful isolation of H pylori from a patient who received triple therapy that failed to eradicate the bacterium.

Inhibitory effect of ketamine on phosphorylation of the extracellular signal-regulated kinase 1/2 following brain ischemia and reperfusion in rats with hyperglycemia.

To determine if the inhibitory effects of ketamine on the extracellular signal-regulated kinase (ERK) 1/2 are involved in reduction of the hyperglycemia-exaggerated cerebral ischemic lesion, rats with normoglycemia, hyperglycemia, or hyperglycemia supplemented with ketamine were subjected to 15 min of forebrain ischemia, and then, reperfusion for 0.5, 1, and 3h. Phosphorylation of ERK1/2 in the brain tissues was assessed by immunohistochemistry and Western blot analysis. In rats with normoglycemia, we demonstrated a moderate increase of the ERK1/2 phosphorylation in the cingulum cortex and hippocampus CA3 following an ischemic intervention. It quickly dropped to control levels after reperfusion for 0.5h. In rats with hyperglycemia, however, the increase of the ERK1/2 phosphorylation in these areas was significantly higher in all animals reperfused. The neuronal death, detected by the TdT-mediated-dUTP nick end labeling assays, was found in the cingulum cortex (5.23+/-2.34, per high power feild) and hippocampus CA3 areas (6.29+/-3.68, per 1mm(2)) in hyperglycemic group after reperfusion for 3h. With ketamine treatment, the ERK1/2 phosphorylation in cingulum cortex and hippocampus CA1 and CA3 areas was found to be the same as that in normoglycemia rats. Our results suggest that hyperglycemia may increase the ischemic insult through modulation of the signal transduction pathways involving ERK1/2. The inhibitory effects of ketamine on the hyperglycemia-activated ERK1/2 phosphorylation are probably through inhibition of the N-methyl d-aspartate-mediated calcium influx, which subsequently reduce the hyperglycemia-exaggerated cerebral damage.

Current status of severe acute respiratory syndrome in China.

Severe acute respiratory syndrome (SARS), also called infectious atypical pneumonia, is an emerging infectious disease caused by a novel variant of coronavirus (SARS-associated coronavirus, SARS-CoV). It is mainly characterized by pulmonary infection with a high infectivity and fatality. SARS is swept across almost all the continents of the globe, and has currently involved 33 countries and regions, including the mainland China, Hong Kong, Taiwan, North America and Europe. On June 30, 2003, an accumulative total reached 8450 cases with 810 deaths. SARS epidemic was very rampant in March, April and May 2003 in the mainland of China and Hong Kong. Chinese scientists and healthcare workers cooperated closely with other scientists from all over the world to fight the disease. On April 16, 2003, World Health Organization (WHO) formally declared that SARS-CoV was an etiological agent of SARS. Currently, there is no specific and effective therapy and prevention method for SARS. The main treatments include corticosteroid therapy, anti-viral agents, anti-infection, mechanical ventilation and isolation. This disease can be prevented and controlled, and it is also curable. Under the endeavor of the Chinese Government, medical staffs and other related professionals, SARS has been under control in China, and Chinese scientists have also made a great contribution to SARS research. Other studies in developing new detection assays and therapies, and discovering new drugs and vaccines are in progress. In this paper, we briefly review the current status of SARS in China.

[In-vitro activity of rabeprazole, lansoprazole, and esomeprazole against Helicobacter pylori].

OBJECTIVE: To investigate the antimicrobial activity of Pariet, Tekpron, Nexium, respectively, against Helicobacter pylori (H. pylori) in vitro. METHODS: Antimicrobial effects of these medicines were evaluated through detection of MICs for 3 H. pylori strains isolated from different countries. RESULTS: The MIC(99) contents were 2.25 mg/L, 42.5 mg/L and 360 mg/L, respectively, for the three medicines. The strains under testing exhibited the same susceptibility to each medicine. Nexium did not inhibit the bacteria under the concentration of 3.6 - 36 mg/L with more and bigger H. pylori colonies seen when compared with controls. CONCLUSIONS: The growth inhibitory activity appeared to be different among the three PPI medicines under investigation, with Rabeprazole the most potential agent of the three. Data suggested that the action of growth inhibition in vitro was resting on the characteristic of the given PPI as well as the supplements of the medicine.