Patients' and caregivers' perspectives of the atopic dermatitis journey.

BACKGROUND: Understanding the patient journey is important to optimize care for patients with atopic dermatitis (AD) and overcome challenges in diagnosis and management. OBJECTIVE: To explore patient and caregiver perspectives regarding their experience with AD. METHODS: Patients and caregivers of patients with AD completed a pre-meeting survey and were invited to join an advisory board meeting in their country (China, Hong Kong, Ireland, Japan and Lebanon) to discuss the survey results. Data were analyzed descriptively. RESULTS: The survey included 31 participants (patients and caregivers) from Hong Kong (n = 7), China (n = 7), Ireland (n = 6), Japan (n = 6) and Lebanon (n = 5). The most challenging factors in the AD journey were management of symptoms before a confirmed diagnosis (68%), sudden recurrence of flares or worsening of symptoms (68%) and lifestyle changes (52%). In terms of overall AD management, 35% of participants indicated that AD was managed well, 23% had a clear treatment plan and 19% were generally satisfied with disease management. A collaborative relationship with healthcare professionals was favored. CONCLUSION: A holistic assessment of AD includes understanding patient and caregiver preferences, needs, experiences and disease perceptions. Addressing the identified gaps may improve the management of AD.

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.

Antimicrobial Resistance of Helicobacter Pylori Among Low-resource Chinese Minorities.

Context: Helicobacter pylori (H. pylori) infection has become a global public-health problem, and people living in low-resource settings may be more likely to be infected because of unhealthy life habits, poor sanitary conditions, and overuse of antibiotics without a prescription. Objectives: The study intended to assess the susceptibility of H. pylori to nine antibiotics commonly prescribed for eradication of H. pylori infections among minority people in Yunnan province, China, to provide updated recommendations for H. pylori eradication therapy among adults. Design: The research team designed a cross-sectional observational study. Setting: The study took place in the First Affiliated Hospital of Kunming Medical University, Yunnan Province. Participants: Participants were 276 people in the Mosuo or Pumi minority population who had lived on the shores of Lugu Lake in Ninglang county, Yunnan province in China for generations. Outcome Measures: After completing a questionnaire, all participants underwent 13C-urea breath test, and those with a positive result participated in an antimicrobial-susceptibility test. For each H. pylori isolate, the research team tested the minimum inhibitory concentrations (MICs) of nine commonly used antibiotics: amoxicillin, azithromycin, levofloxacin, clarithromycin, metronidazole, tetracycline, rifampicin, gentamicin, and moxifloxacin. Results: The research team confirmed that 276 participants were resistant to at least one antibiotic. The resistances rates for moxifloxacin, metronidazole, and levofloxacin were the highest, while that for amoxicillin was the lowest, and no isolates were resistant to gentamicin. Double resistance (33.20%) had the highest proportion of all multiple-resistance patterns. Moreover, the metronidazole resistance rate was higher in females than in males and in nonsmokers than in smokers, and rifampicin resistance was higher in nondrinkers than in drinkers, suggesting that smoking and drinking might be protective against metronidazole and rifampicin resistance. Conclusions: Most of the Mosuo and Pumi people in Yunnan were resistant to antibiotics. Moxifloxacin, metronidazole, and levofloxacin should no longer be the main medicines for H. pylori, whereas amoxicillin and gentamicin should be recommended to be the first-line clinical therapy for H. pylori eradication regimens.

Effects of Swallowing Rehabilitation Training with a Balloon Dilation Therapy on the Deglutition Function and Quality of Life of Patients with Dysphagia after Radiotherapy for Nasopharyngeal Carcinoma.

Objective: The aim of this study is to investigate the effects of swallowing rehabilitation training with a balloon dilation therapy on the deglutition function and quality of life of patients with dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The study was a retrospective study. The data of the 100 patients with dysphagia after NPC radiotherapy in our hospital between April 2021 and April 2022 were retrospectively analyzed. The patients were separated into the control group (n = 50) and experimental group (n = 50) according to their different treatments that were balloon dilation for the former and balloon dilation with swallowing rehabilitation training for the latter. The deglutition function, which was comprehensively evaluated by Kubota's water swallow test and assessments of penetration/aspiration and pharyngeal residue, and quality of life were compared between the two groups. Results: The scores of Kubota's water swallow test, penetration aspiration scale (PAS), and Yale pharyngeal residue severity rating scale (YPR-SRS) in the experimental group after treatment were (2.04 ± 0.66), (2.92 ± 1.07), and (2.42 ± 0.90), respectively, which were remarkably lower than (2.58 ± 0.78), (4.38 ± 1.51), and (2.78 ± 0.86) in the control group, with distinct differences in the data between both the groups (P < 0.05). The quality of life of patients in the experimental group was distinctly better than that in the control group (P < 0.001). Conclusion: Swallowing rehabilitation training in combination with a balloon dilation therapy can improve the deglutition function in patients with dysphagia after NPC radiotherapy as well as their quality of life, with a clinical application value.

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.

Hugan tablets for the treatment of RUCAM based drug-induced liver injury: a propensity score matching analysis using a nationwide database.

BACKGROUND: Drug-induced liver injury (DILI) is a major clinical challenge with no specific therapeutic drugs available. It is crucial to develop new agents to improve the clinical outcome of patients with DILI. This study evaluated the efficacy and safety of Hugan tablets in DILI patients using a nationwide database. RESEARCH DESIGN AND METHODS: We analyzed the clinical data of DILI patients from a nationwide DILI database (www.hepatox.org). Patients who received oral Hugan tablets for DILI were defined as the Hugan group, and those who received no treatment for DILI were defined as the control group. RESULTS: There were 111 cases in the Hugan group and 512 cases in the control group. One-to-one propensity score matching created 111 matched pairs. The normalization rates of alanine aminotransferase and aspartate aminotransferase in the Hugan group were significantly higher than those in the control group (50.45% vs. 26.13%, p ≤ .0002 and 67.57% vs. 41.75%, p ≤ .0001). There were no differences in the incidence of renal function impairment or blood abnormality between the two groups. CONCLUSIONS: Hugan tablets are safe and effective in DILI treatment. Large-scale randomized controlled studies are needed to explore the effects of Hugan tablets on DILI induced by different offending drugs. TRIAL REGISTRATION: The study protocol was posted on ClinicalTrials.gov with NCT number: NCT02407964.

Selenium attenuates ischemia/reperfusion injury­induced damage to the blood­brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway­mediated autophagy inhibition.

Ischemic stroke is a leading cause of mortality and disability. Diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood­brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague­Dawley rats. Treatment with selenium and the autophagy inhibitor 3­methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy­related proteins (P<0.05). In addition, selenium increased the phosphorylation levels of PI3K, AKT and mTOR (P<0.05). A mouse bEnd.3 brain microvascular endothelial cell line was co­cultured in vitro with an MA­h mouse astrocyte­hippocampal cell line to simulate the BBB. The cells were then subjected to hyperglycemia, followed by oxygen­glucose deprivation for 1 h and reoxygenation for 24 h. It was revealed that selenium increased TJ protein levels, reduced BBB permeability, decreased autophagy levels and enhanced the expression of phosphorylated (p)­AKT/AKT and p­mTOR/mTOR proteins (P<0.05). Treatment with wortmannin (an inhibitor of PI3K) significantly prevented the beneficial effects of selenium on the BBB, whereas insulin­like growth factor 1 (a PI3K activator) mimicked the effects of selenium. In conclusion, the present findings indicated that selenium can inhibit autophagy by regulating the PI3K/AKT/mTOR signaling pathway, significantly preventing BBB damage following cerebral I/R injury in hyperglycemic conditions.

Randomized clinical trial of combined therapy with oral α-lipoic acid and NB-UVB for nonsegmental stable vitiligo.

Vitiligo is associated with oxidant stress and α-lipoic acid (ALA) is an antioxidative agent. To evaluate the efficacy and safety of oral ALA in combination with NB-UVB phototherapy on nonsegmental stable vitiligo. The prospective, multi-center, parallel controlled, double-blind randomized clinical trial was conducted from 2012 to 2014, in seven comprehensive tertiary hospitals in China. The patients were randomized into oral ALA group or placebo group at a dose of 300 mg daily for 6 months. All of them received NB-UVB phototherapy three times weekly. The repigmentation rate was evaluated by 4-point grading scale of improvement: >98%, 50-98%, 10-49%, <10%. A total of 133 patients were enrolled in the study, including 72 cases in treatment group and 61 cases in control group. In treatment group, 2.04% (1/49) patients achieved ≥50% improvement at 1-month after enrollment (M1), and the percentage of patients increased to 8.51% (4/47), 14.0% (6/43), and 37.8% (14/37) at M2, M3, and M6, respectively. In control group, the percentages were similar at all timepoints. No significant difference was seen between the two groups (P > .05). For elder patients, younger patients, male or female, no significant differences were found between treatment group and control group at all timepoints. ALA did not show additional benefit to NB-UVB therapy in the treatment of nonsegmental stable vitiligo. More studies should be done to identify other protocols of ALA or other types of antioxidants for stable vitiligo.

Palmatine ameliorates Helicobacter pylori-induced chronic atrophic gastritis by inhibiting MMP-10 through ADAM17/EGFR.

Palmatine (Pal), a plant-based isoquinoline alkaloid, was initially isolated from Coptidis Rhizoma (CR, Huanglian in Chinese) and considered to be a potential non-antibiotic therapeutic agent that can safely and effectively improve Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). However, underlying mechanisms are unclear. In this study, we explored the protective effect of Pal on H. pylori induced CAG in vivo and in vitro. As a result, Pal alleviated the histological damage of gastric mucosa and the morphological changes of gastric epithelial cell (GES-1) caused by H. pylori. Furthermore, Pal significantly inhibited the expression of EGFR-activated ligand genes, including a disintegrin and metalloproteinase 17 (ADAM17) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), and the proinflammatory factors, such as chemokine 16 (CXCL-16) and interleukin 8 (IL-8), were suppressed. In addition, Pal attenuated inflammatory infiltration of CD8+ T cells while promoted Reg3a expression to enhance host defense. Taken together, we concluded that Pal attenuated the MMP-10 dependent inflammatory response in the gastric mucosa by blocking ADAM17/EGFR signaling, which contributed to its gastrointestinal protective effect.

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing.

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: A phase II trial.

BACKGROUND: Drug-induced liver injury (DILI) is the most common reason for a drug to be withdrawn from the market. Apart from stopping the offending drug, no regimens are available for treating idiosyncratic DILI in clinical practice. METHODS: We carried out a randomized, double-blind, multidoses, active drug controlled, multicentre phase II trial to assess the safety and efficacy of the study drug, magnesium isoglycyrrhizinate (MgIG), as compared to tiopronin, a standard therapy for DILI in China. The primary outcome was the proportion of alanine aminotransferase (ALT) normalization at week 4 after study drug administration. Logistic regression was used to examine the odds of ALT normalization between low dose (Group A) and high dose (Group B) vs active control (Group C). RESULTS: One hundred and seventy-four eligible subjects were randomized and enrolled into three groups: 59 in group A, 56 in group B and 59 in group C. It was shown that group A and group B lowered ALT level even at early stage of study drug administration; when compared with Group C (61.02%), the proportions of ALT normalization at week 4 were significantly greater in Group A (84.75%, P = .0029) and Group B (85.71%, P = .0037) respectively. The results from the univariate logistic model showed that the odds of ALT normalized among subjects in Group A were about 3.6 times greater (OR = 3.55, 95% CI: 1.47-8.57, P = .0049) than subjects in Group C. Similar effect was observed among subjects in Group B (OR = 3.83, 95% CI: 1.54-9.55, P = .0039). CONCLUSIONS: This trial provided preliminary evidence that MgIG is an effective and safe treatment for patients with acute DILI.

Tetra-arsenic tetra-sulfide ameliorates lupus syndromes by inhibiting IL-17 producing double negative T cells.

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra-arsenic tetra-sulfide (As4 S4 ), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus-prone mice treated with As4 S4 has showed improved monocytosis, decreased serum interleukin (IL)-6 and suppressed skin, liver and renal lesions with well-tolerance. In this study, we explored the effect and mechanism of As4 S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4 S4 treatment groups and dosed with As4 S4 or placebo for 8 weeks. We found that As4 S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4 S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL-17, IL-10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4 S4 treated MRL/lpr mice. Taken together, As4 S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL-17, which may be produced by DN T cells. As4 S4 may represent a new therapy for SLE.

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.

Selenium, aging and aging-related diseases.

Selenium is an essential trace element in the human body and plays an important role in the body via selenoprotein, which contains selenium. Selenoproteins (glutathione peroxidase, thioredoxin reductase, methionine sulfoxide reductase1 and endoplasmic reticulum-selenoproteins, etc.) have antioxidant effects and are involved in regulating antioxidant activities. Aging is an inevitable process and is always accompanied by aging-related diseases. Reactive oxygen species are important initial factors in aging and aging-related diseases. Selenium contributes to the alleviation of reduced reactive oxygen species-mediated inflammation, reduced DNA damage and prolonged telomere length and thereby plays roles in fighting aging and preventing aging-related diseases. In the elderly, aging-related diseases include neuropsychiatric diseases, tumors, cardiovascular diseases, and skin aging, among others. Selenium supplementation is an important strategy for anti-aging and the prevention of aging-related diseases and is of great significance for the elderly. However, with the accumulation of related research, selenium supplementation does not necessarily contribute to the prevention of aging and aging-related diseases. It is believed that a low level of selenium is beneficial to the human body. Thus, the effect of selenium on human aging and aging-related diseases is still controversial. This paper reviews the research progress and objective role of selenium in aging and aging-related diseases.

Application of an individualized and reassemblable 3D printing navigation template for accurate puncture during sacral neuromodulation.

OBJECTIVE: To evaluate the feasibility and safety of an individualized and reassemblable three-dimensional (3D) printing navigation template for making accurate punctures during sacral neuromodulation (SNM). METHODS: From July 2016 to July 2017, 24 patients undergoing SNM were enrolled. Conventional X-ray guidance was used in the control group, which included 14 patients, while the 3D printing template was used in the experimental group, which included 10 patients. The number of punctures, the average puncture time, the exposure to X-ray, the adjustment time during the operation and the testing of the SNM device, the infection and haemorrhage rate, and the implantable pulse generator (IPG) implantation rates were compared between the two groups. RESULTS: In total, 24 patients successfully underwent stage I. When comparing the control group and the experimental group, the number of punctures were 9.6 ± 7.7 and 1.5 ± 0.7, respectively; the average puncture times were 35.4 ± 14.6 and 4.1 ± 2.2 min, respectively; and the X-ray exposure levels were 8.37 ± 4.83 mAs and 2.34 ± 0.54 mAs, respectively. No postoperative complications were reported in either group. The IPG implantation rates were not different between the two groups. CONCLUSION: The 3D printing template for SNM can help us to perform accurate and quick punctures into the target sacral foramina, reduce X-ray exposure, and shorten the operation time. For patients with obesity, sacral variation, sacral bone fractures or losses and for patients who are unable to tolerate the prone position during operation, use of the 3D printing template is recommended.

[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.