Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

A Case of Vitiligo Combined with Systemic Lupus Erythematosus Treated with Tofacitinib.

Vitiligo is a skin depigmentation disease resulting from melanocyte destruction and often co-occurring with autoimmune disorders like hyperthyroidism, alopecia areata, pernicious anemia, and systemic lupus erythematosus (SLE). Although various traditional treatments exist for vitiligo, their effectiveness varies considerably. This report presents a unique case of a vitiligo patient with concomitant systemic lupus erythematosus. Remarkably, after a 30-day course of treatment with tofacitinib, complete repigmentation of the white macular rash was achieved, and there were no adverse drug reactions. These findings provide compelling evidence for the efficacy and safety of oral JAK inhibitors, such as tofacitinib, in vitiligo treatment. Additionally, JAK inhibitors can yet be regarded as a promising new treatment option for vitiligo patients with concurrent autoimmune diseases.

Impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease patients complicated with end-stage renal disease.

It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.

Acquired Digital Fibrokeratoma: A Report of Five Cases and Review of the Literature.

Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported. The mean age at onset was 42.6 years, and the mean disease duration was 3 years. Four patients had ADF on the hands, and 1 patient had ADF on the foot. The clinical manifestations were all solitary, skin-colored papules, with a firm texture and smooth surface, protruding from the skin surface. In 3 patients, ADF manifested as columnar protrusions, and in 2 patients, ADF manifested as dome-shaped protrusions. For all 5 patients, the diameters of the lesions were <1 cm. Clinically, all 5 patients were misdiagnosed (ie, eccrine poroma (EP), common warts, rudimentary polydactyly, pyogenic granuloma (PG), and acral fibroma). All cases of ADF were confirmed by histopathology. The histopathological manifestations of ADF were as follows: finger-like protrusions on the skin surface; collagen fiber bundles running vertically to the epidermis seen in the dermis; and thick red-stained collagen fibers connected with the normal dermal connective tissue below. All 5 patients underwent surgical resection; the distance between the incision margin and the edge of the tumor was 2-3 mm, and the surgical depth was the deep dermis. No recurrence was observed in more than half a year of follow-up after surgery.

The Potential Predicting Value of D-Dimer to Fibrinogen Ratio on Functional Outcome at 1 Year after Acute Ischemic Stroke: A Longitudinal Study.

INTRODUCTION: Previous studies have suggested that the D-dimer to fibrinogen ratio (DD/Fg) could be a potential predictor for deep vein thrombosis, pulmonary embolism, and stroke severity. However, the association between plasma DD/Fg and functional outcome following acute ischemic stroke (AIS) has been unclear. METHODS: Our study followed the STROBE guideline and used a prospective cohort design to investigate this association. A total of 454 patients with AIS were enrolled consecutively in our study, and the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were assessed for stroke severity and functional outcome, respectively. RESULTS: We found a significant difference in DD/Fg values between the three groups based on NIHSS scores at admission. Specifically, the DD/Fg values were higher in the poor functional outcome group (mRS score of 2-6) compared to the favorable functional outcome group (mRS score of 0-1) at the 1-year follow-up (p < 0.001). Additionally, the DD/Fg values were independently associated with poor functional prognosis at 1 year following the onset of stroke, even after adjusting for potential confounders (OR 9.21, 95% CI, 3.68-23.02, p < 0.001). CONCLUSIONS: Our findings suggest that DD/Fg values at admission may serve as risk predictors for poor functional outcomes in patients with AIS 1 year after the stroke.

Oxidative Stress in Diabetic Peripheral Neuropathy: Pathway and Mechanism-Based Treatment.

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.

Zuogui-Jiangtang-Yishen decoction prevents diabetic kidney disease: Intervene pyroptosis induced by trimethylamine n-oxide through the mROS-NLRP3 axis.

BACKGROUND: Nowadays, diabetic kidney disease (DKD) has become one of the most threatening to the end-stage renal diseases, and the early prevention of DKD is inevitable for Diabetes Mellitus (DM) patients. AIMS: Pyroptosis, a programmed cell death that mediates renal inflammation induced early renal injury. The trimethylamine n-oxide (TMAO) was also an independent risk factor for renal injury. Here, the associations between TMAO-induced pyroptosis and pathogenesis of DKD were studied, and the potential mechanism of Zuogui-Jiangtang-Yishen (ZGJTYS) decoction to prevent DKD was further investigated. METHOD: Using Goto-Kakizaki (GK) rats to establish the early DKD models. The 16S-ribosomal RNA (16S rRNA) sequencing, fecal fermentation and UPLC-MS targeted metabolism techniques were combined to explore the changes of gut-derived TMAO level under the background of DKD and the effects of ZGJTYS. The proximal convoluted tubule epithelium of human renal cortex (HK-2) cells was adopted to explore the influence of pyroptosis regulated by TMAO. RESULTS: It was demonstrated that ZGJTYS could prevent the progression of DKD by regulating glucolipid metabolism disorder, improving renal function and delaying renal pathological changes. In addition, we illustrated that gut-derived TMAO could promote DKD by activating the mROS-NLRP3 axis to induce pyroptosis. Furthermore, besides interfering with the generation of TMAO through gut microbiota, ZGJTYS inhibited TMAO-induced pyroptosis with a high-glucose environment and the underlying mechanism was related to the regulation of mROS-NLRP3 axis. CONCLUSION: Our results suggested that ZGJTYS inhibited the activation of pyroptosis by gut-derived TMAO via the mROS-NLRP3 axis to prevent DKD.

Single-Cell and Spatial Transcriptomics Decodes Wharton's Jelly-Derived Mesenchymal Stem Cells Heterogeneity and a Subpopulation with Wound Repair Signatures.

The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ-MSCs) may be responsible for the poor clinical outcomes and poor reproducibility of treatments based on WJ-MSCs. Exploration of WJ-MSC heterogeneity with multimodal single-cell technologies will aid in establishing accurate MSC subtyping and developing screening protocols for dominant functional subpopulations. Here, the characteristics of WJ-MSCs are systematically analyzed by single cell and spatial transcriptome sequencing. Single-cell transcriptomics analysis identifies four WJ-MSC subpopulations, namely proliferative_MSCs, niche-supporting_MSCs, metabolism-related_MSCs and biofunctional-type_MSCs. Furthermore, the transcriptome, cellular heterogeneity, and cell-state trajectories of these subpopulations are characterized. Intriguingly, the biofunctional-type MSCs (marked by S100A9, CD29, and CD142) selected in this study exhibit promising wound repair properties in vitro and in vivo. Finally, by integrating omics data, it has been found that the S100A9+ CD29+ CD142+ subpopulation is more enriched in the fetal segment of the umbilical cord, suggesting that this subpopulation deriving from the fetal segment may have potential for developing into an ideal therapeutic agent for wound healing. Overall, the presented study comprehensively maps the heterogeneity of WJ-MSCs and provides an essential resource for future development of WJ-MSC-based drugs.

User acceptance of smart home voice assistant: a comparison among younger, middle-aged, and older adults.

Voice assistants are widely used in smart home environments. This study aimed to investigate user acceptance of a smart home voice assistant. A questionnaire was designed, and 471 Chinese adults were recruited to complete the questionnaire. The data were analyzed using exploratory factor analysis and regression analysis. The results revealed that user requirements of adults were composed of six factors: hedonic motivation and trust (ß = .41, p < .001), social influence (ß = .22, p < .001), performance expectancy (ß = .15, p < .001), effort expectancy (ß = .08, p = .018), product features (ß = .15, p = .009), and facilitating conditions (ß = .06, p = .049). Among these six factors, hedonic motivation and trust are considered the most important. Younger, middle-aged, and older adults differed significantly in their requirements and acceptance of a smart home voice assistant. These findings have implications for the design of smart home voice assistants so that they are more acceptable to younger and older adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s10209-022-00936-1.

Metabolic control of innate lymphoid cells in health and disease.

Innate lymphoid cells (ILCs) are a family of predominantly tissue-resident lymphocytes that critically orchestrate immunity, inflammation, tolerance and repair at barrier surfaces of the mammalian body. Heterogeneity among ILC subsets is comparable to that of adaptive CD4+ T helper cell counterparts, and emerging studies demonstrate that ILC biology is also dictated by cellular metabolism that adapts bioenergetic requirements during activation, proliferation or cytokine production. Accumulating evidence in mouse models and human samples indicates that ILCs exhibit profound roles in shaping states of metabolic health and disease. Here we summarize and discuss our current knowledge of the cell-intrinsic and cell-extrinsic metabolic factors controlling ILC responses, as well as highlight contributions of ILCs to organismal metabolism. It is expected that continued research in this area will advance our understanding of how to manipulate ILCs or their metabolism for therapeutic strategies that benefit human health.

Clinical application of the CO2 laser in Ab externo Schlemm's canal surgery.

Purpose: This study aimed to investigate the clinical application of laser as a knife in Ab externo Schlemm's canal (SC) surgery and compare the efficacy and safety of the CO2 laser with the conventional procedure using a surgical knife. Methods: Patients who underwent either canaloplasty or trabeculotomy with CO2 laser system which was used to locate and ablate the outer wall of SC at the time interval between May 2020 and May 2021 were identified, their medical files were reviewed, and their results were compared with conventional surgery group who underwent canaloplasty or trabeculotomy with conventional surgical knife at the same time period. The following datas were conducted and compared: age, sex, intraocular pressure (IOP), number of drugs, best-corrected visual acuity (BCVA), mean deviation and pattern standard deviation of visual field examination, SC opening related complications. Results: A total of 49 patients (49 eyes) were included in this study, including 23 in the Laser surgery group and 26 in the conventional surgery group. Time for SC opening was 49.33 ± 25.23 s and 116.50 ± 31.79 s for laser surgery group and conventional surgery group, respectively. This difference between the two groups was statistically significant (P < 0.01). Hemorrhage occurred in five eyes during ablation for the laser surgery group and in 24 eyes for the conventional surgery group. In addition, anterior chamber penetration occurred in two cases for the laser surgery group and in six cases for the conventional surgery group. The success rate of identifying and opening outer wall of SC was 91.30% (21 eyes) for the laser surgery group and 76.92% (20 eyes) for the conventional surgery group. The difference between preoperative and postoperative intraocular pressure for each group was statistically significant (P < 0.01), and there were no statistically significant differences across the two groups in terms of postoperative IOP (P = 0.238) and BCVA (P = 0.389). Conclusion: Compared with the conventional procedure using a surgical knife, CO2 laser-assisted ablation of the outer wall of SC was less time-consuming and less technically challenging. CO2 laser-assisted ablation also resulted in fewer complications. Furthermore, it had a shorter learning curve and a higher success rate of identifying and opening SC.

Recurrent herpes zoster in a rheumatoid arthritis patient treated with tofacitinib: A case report and review of the literature.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis (RA). Varicella zoster virus reactivation leading to herpes zoster (HZ) is an adverse effect of this drug; however, recurrent HZ at the same site is a rare clinical condition. CASE SUMMARY: A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment (10 mg daily). About 1 mo after initiation of oral tofacitinib, she developed blisters on the left flank and abdomen and was diagnosed with HZ; antiviral therapy with acyclovir was resolutory. However, 5 d prior to presentation at our hospital, erythema and blisters with severe pain recurred at the same site. Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum, with a pain score of 8 (visual analogue scale). Antiviral, nutritional supplement, analgesic and other treatments led to healing but over an atypically long period (approximately 26 d, vs approximately 1 wk). HZ is a common and serious adverse reaction of JAK inhibitors, but it rarely recurs. Our patient's experience of HZ recurrence at the same site, with a wider affected area, more severe pain and longer healing period, is inconsistent with previous reports. CONCLUSION: Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment, with more severe clinical manifestations than in the initial occurrence.

Determinants of Diabetic Peripheral Neuropathy and Their Clinical Significance: A Retrospective Cohort Study.

Background: In this study, we investigated the epidemiological characteristics and predictors of diabetic peripheral neuropathy (DPN) in adult patients with type 2 diabetes mellitus (DM). Methods: The study was designed as a retrospective cohort trial at the First Affiliated Hospital of Wenzhou Medical University. From January 2017 to December 2020, a total of 1,262 patients with DM were enrolled to assess the risk factors for DPN. The patients were divided into two groups (DPN group and non-DPN group). The Mann-Whitney U test or t-test, receiver operating characteristic (ROC) analyses, univariate chi-square analyses, and multiple logistic regression analyses were used to analyze the adjusted predictors of DPN. Results: The overall prevalence of DPN in DM patients was 72.7% (n = 793/1,091). Multivariate analysis revealed that age > 66 years (odds ratio [OR], 2.647; 95% confidence interval [CI] 1.469-4.770; p = 0.002), history of hypertension (OR, 1.829; 95% CI 1.146-2.920; p = 0.011), neutrophil (NE) levels exceeding 4.0 × 109/L (OR 0.256; 95% CI 0.162-0.405; p = 0.001), lymphocyte (LY) levels over 3.0 × 109/L (OR 7.173; 95% CI 4.258-12.086; p = 0.000), HbA1c > 7.7% (OR 3.151; 95% CI 1.959-5.068; p = 0.000), and FT3 > 4.4 pmol/L (OR 0.417; 95% CI 0.263-0.662; p = 0.000) were six significant predictive factors for the prevalence of DPN. Conclusions: High levels of LY, HbA1c, history of hypertension, and > 66 years of age increase the risk of DPN in adult patients with DM, while high levels of NE and FT3 were protective factors of DPN. Thus, the prediction of DPN can significantly be improved by identifying older patients over the age of 66 and history of hypertension, as well as establishing the biochemical cutoff values of NE, LY, HbA1c, and FT3.

Granular Parakeratosis: A Case Report.

Granular parakeratosis is an uncommon acquired keratinization disorder that occurs in the armpit, groin, and other parts of the body. It may be related to stimulation by detergents and antiperspirants. This article reports a case of granular parakeratosis in the groin. The patient was a young man with no predisposing factors. The clinical manifestations included symmetrical bilateral inguinal erythema, dryness, and a small amount of bran-like desquamation. After histopathological examination, the final diagnosis was granular parakeratosis, which was cured by topical application of glucocorticoid cream and silicone oil cream. Granular parakeratosis is a rare skin disease of unknown etiology. Clinicians need to pay attention to this disease and differentiate it from various diseases to avoid misdiagnosis.

Entropy analysis and grey cluster analysis of multiple indexes of 5 kinds of genuine medicinal materials.

5 kinds of genuine medicinal materials, including Diding (Latin name: Corydalis bungeana Turcz), Purslane (Latin name: Portulaca oleracea L.), straw sandal board (Latin name: Hoya carnosa (L.f.) R. Br), June snow (Latin name: Serissa japonica (Thunb.) Thunb.), pine vine rattan (Latin name: Lycopodiastrum casuarinoides (Spring) Holub. [Lycopodium casuarinoides Spring]), were selected as the research objects. The combustion heat, thermo gravimetric parameters, and fat content, calcium content, trace element content, ash content of 5 kinds of genuine medicinal materials were measured. The combustion heat, differential thermal gravimetric analysis, fat content, calcium content, trace elements content, and ash content of 5 kinds of genuine medicinal materials were used to build a systematic multi-index evaluation system by gray pattern recognition and grey correlation coefficient cluster analysis, which can make up for the gaps in this area and provide scientific basis and research significance for the study of genuine medicinal materials quality. The results showed that the order of combustion heat of 5 kinds of genuine medicinal materials, including Diding, Purslane, straw sandal board, June snow, pine vine rattan, was Diding > June snow > straw sandal board > Purslane > pine vine rattan, the order of fat content (%) of 5 kinds of genuine medicinal materials was straw sandal board > Diding > pine vine rattan > June snow > Purslane, the order of calcium content (%) was pine vine rattan > June snow > Purslane > straw sandal board > Diding, the order of ash content was June snow > Purslane > straw sandal board > pine vine rattan > Diding. From the analysis of thermogravimetric analysis results and thermogravimetric combustion stability, the order of combustion stability of 5 kinds of genuine medicinal materials was June snow > pine Vine rattan > straw sandal board > Diding > Portulaca oleracea. The order of the content of 12 trace elements in 5 kinds of genuine medicinal materials, in terms of trace element content, June snow contains the highest trace elements in all samples. According to combustion heat, combustibility (combustion stability of genuine medicinal materials), fat, calcium, ash, trace element content, the comprehensive evaluation results of multi-index analysis constructed by gray correlation degree, gray correlation coefficient factor analysis, and gray hierarchical cluster analysis showed that the comprehensive evaluation multi-index order of 5 genuine medicinal materials, including Diding, Purslane, straw sandal board, June snow and pine vine rattan, was June snow > straw sandal board > Diding > Purslane > pine vine rattan. Therefore, the comprehensive evaluation results of the quality of genuine medicinal materials selected in this study were June snow the best, followed by straw sandal board. This research has important theoretical and practical significance for the multi-index measurement and comprehensive evaluation of genuine medicinal materials, and can provide scientific basis and research significance for the research of multi-index quality control of genuine medicinal material.

Sex differences in microstructural alterations in the corpus callosum tracts in drug-naïve children with ADHD.

Widespread alterations in the corpus callosum (CC) microstructure and organization have been found in children with attention-deficit/hyperactivity disorder (ADHD); however, few studies have investigated the diffusion characteristics and volume of transcallosal fiber tracts defined by specific cortical projections in ADHD, which is important for identifying distinct functional interhemispheric connection abnormalities. In the current study, an automated fiber-tract quantification (AFQ) approach based on diffusion tensor imaging identified seven CC tracts according to their cortical projections and estimated diffusion parameters and volume among 76 drug-naïve ADHD patients (53 boys and 23 girls) and 37 typically developing children (TDC) (20 boys and 17 girls) matched for age, IQ, and handedness. We found significantly lower fractional anisotropy (FA) in the occipital and superior parietal tracts and higher mean diffusivity (MD) in the posterior, superior parietal and anterior frontal tracts in children with ADHD compared with TDC. In addition, lower FA and higher radial diffusivity (RD) in the occipital callosal tract were significantly associated with higher hyperactivity and impulsivity performance in ADHD. In addition, sex-by-diagnosis interactions were observed in the occipital, posterior and superior parietal tracts. Girls with ADHD showed decreased FA and volume in the occipital tract, which were significantly associated with increased impulsivity performance and poor response control, and increased MD in the posterior and superior parietal callosal tracts, which were significantly associated with increased inattention performance, whereas boys with ADHD merely showed decreased volume in the frontal tract. Our results elucidated that sex-specific alterations in the CC tracts potentially underlie ADHD symptomatology and further suggested a differential contribution of abnormalities in different CC tracts to impulsivity and inattention among girls with ADHD.

Different effects of the DRD4 genotype on intrinsic brain network connectivity strength in drug-naïve children with ADHD and healthy controls.

The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.

Effects of antidepressant medicines on preventing relapse of unipolar depression: a pooled analysis of parametric survival curves.

BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.

Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway.

The mechanisms underlying the development of neuropathy associated with diabetes mellitus are not fully understood. Resveratrol, as a nonflavonoid polyphenol, plays a variety of beneficial roles in the treatment of chronic diseases such as Alzheimer's disease, coronary heart disease and obesity. In our study, the role of nuclear erythroid 2-related factor 2 (Nrf2) in resveratrol-mediated protection against streptozotocin-induced diabetic peripheral neuropathy (DPN) was investigated, and the antioxidant effect of resveratrol in diabetic peripheral nerves was studied. The STZ-treated model mice were divided into two groups. The resveratrol group was intragastrically administered 10 ml/kg 10% resveratrol once a day until the 12th week after STZ injection. The vehicle-treated mice were injected with the same volume of DMSO. Analysis of the effects of resveratrol in DPN revealed the following novel findings: (i) the pain and temperature sensitivities of diabetic mice were improved after treatment with resveratrol; (ii) Nrf2 expression was increased in the diabetic peripheral nerves of resveratrol-treated mice, and NF-KB pathway inhibition protected nerves upon resveratrol treatment in peripheral neuropathy; and (iii) resveratrol modulated the anti-inflammatory microenvironment of peripheral nerves by increasing Nrf2 activation and the expression of p-p65, and these changes may have been responsible for the neuroprotective effect of resveratrol in DPN, which was confirmed by Nrf2 knockout in diabetic mice. Overall, this study demonstrates that resveratrol may attenuate the severity of DPN by protecting peripheral nerves from apoptosis by inhibiting the NF-KB pathway and increasing Nrf2 expression.

Association of platelet count and plateletcrit with nerve conduction function and peripheral neuropathy in patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Diabetes has been considered as a 'pro-thrombotic state' with enhanced platelet reactivity. Abnormality in platelet aggregation has been found in patients with its most common chronic complication - diabetic peripheral neuropathy (DPN). The purpose of this study was to investigate the potential association of platelet indices with nerve conduction function and the presence of DPN in Chinese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This study involved a total of 211 inpatients with type 2 diabetes mellitus and 55 healthy individuals for whom nerve conduction studies were carried out. DPN was diagnosed according to the American Diabetes Association recommendation. Clinical data were retrospectively collected. RESULTS: Patients with diabetes in whom neuropathy developed had lower levels of platelet count (PLT) and plateletcrit (PCT) than healthy controls (P < 0.05). Statistically significant associations of low PLT and PCT levels with the reduction of summed amplitude/velocity Z-score, and the prolongation of F-wave minimum latency in nerve conduction studies were found. Furthermore, after multivariate adjustment, logistic regression analysis showed that low levels of PLT (odds ratio 2.268, 95% confidence interval 1.072-4.797; P < 0.05; PLT <226 vs PLT ≥226) and PCT (odds ratio 2.050, 95% confidence interval 1.001-4.201; P < 0.05; PCT <0.222 vs PCT ≥0.222) in type 2 diabetes mellitus patients were risk factors for the presence of DPN. CONCLUSIONS: Lower PLT and PCT levels are closely associated with poorer peripheral nerve conduction functions and the presence of neuropathy in patients with type 2 diabetes mellitus, which suggests that PLT and PCT might be potential biomarkers for showing DPN.