Comparison of two swept-source optical coherence tomography devices, a Scheimpflug camera system and a ray-tracing aberrometer in the measurement of corneal power in patients with cataract.

PURPOSE: To assess the differences and similarities in the corneal curvature obtained by two swept-source optical coherence tomography (SS-OCT) devices, Scheimpflug imaging system and one ray tracing aberrometer in patients with cataracts. Moreover, this study aimed to compare the differences in posterior corneal (PK), total corneal (TK) and true net power (TNP) measurements among the IOLMaster 700, CASIA2, and Pentacam. METHODS: A total of 200 eyes of 200 patients (116 female, 58%) were enrolled in this study, with a mean age of 65.9 ± 9.5 years. The flattest (Kf), steepest (Ks), and mean cornal powers (Km), J0, and J45 were obtained using two SS-OCT-based biometric devices, one rotating camera system and one ray-tracing aberrometer. The PK, TK and TNP values were also measured using these devices. To evaluate the differences and similarities between the devicves, the Friedman test, Pearson correlation coefficient (r), intraclass coefficient correlation (ICC) and Bland‒Altman plots with 95% limits of agreement (LoA) were used, and boxplots and stacked histograms were generated to describe the distributions of the data. RESULTS: There were no significant differences between the IOLMaster 700 and Pentacam for any of the keratometry values. Additionally, there were no significant differences between the IOLMaster 700 and iTrace in evaluating J0 and J45. Bland‒Altman plots revealed relatively wide LoA widths, almost larger than 1 diopter for the keratometry values and almost larger than 0.5 diopter for J0 and J45 values among the four devices. In terms of PK and TK values, significant differences and low ICCs were found among the three devices. CONCLUSIONS: Although strong correlations and good agreement were found among the IOLMaster700, CASIA2, Pentacam and iTrace for Kf, Ks, Km and J0, J45, it seems that the measurements should not be used interchangeably because of the wide LoA widths and the presence of significant differences among the devices. Similarly, due to significant differences and low ICCs, the PK, TK and TNP values obtained by IOLMaster 700, CASIA2, and Pentacam should not be used interchangeably.

Factors predicting depressive symptoms in parents of children with autism spectrum disorder in eastern China.

BACKGROUND: Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms. METHODS: A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD. RESULTS: A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026-7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234-8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108-5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093-1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201-0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221-0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950-0.996) were less likely to have depressive symptoms. CONCLUSIONS: Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

Physical cleansing reduces the mindset effect in problem-solving.

The present study investigated whether physical cleansing can reduce the mindset effect in problem-solving in two experiments. Both experiments followed the same procedure. In the first stage, participants formed a mindset through the Luchins' water-jar task (Experiment 1) or the idiom maze task (Experiment 2). The second stage is cleansing manipulation. In Experiment 1, participants were asked to clean their hands with wipes (cleansing condition) or examine the packaging of the wipes (no-cleansing condition). In Experiment 2, participants were asked to watch a washing-hands video (cleansing condition) or watch an examining-pen video (no-cleansing condition). At last, all participants completed the mindset effect test problems. The results showed that the participants in the cleansing condition were less affected by the mindset than those in the no-cleansing condition, indicating that physical cleansing reduced the mindset effect. Our results provide new evidence for the clean-slate effects and support the hypothesis that physical cleansing is an embodied process of psychological separation.

Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.

Mitochondrial damage in a Takotsubo syndrome-like mouse model mediated by activation of ß-adrenoceptor-Hippo signaling pathway.

Takotsubo syndrome (TTS) is characterized by short-term contractile dysfunction with its mechanism undefined. We showed that activation of cardiac Hippo pathway mediates mitochondrial dysfunction and that stimulation of ß-adrenoceptors (ßAR) activates Hippo pathway. Here, we investigated the role of ßAR-Hippo signaling in mediating mitochondrial dysfunction in isoproterenol (Iso)-induced TTS-like mouse model. Elderly postmenopausal female mice were administered with Iso (1.25 mg/kg/h for 23 h). Cardiac function was determined by serially echocardiography. At days 1 and 7 post-Iso exposure, mitochondrial ultrastructure and function were examined by electron microscopy and various assays. Alterations in cardiac Hippo pathway and effects of genetic inactivation of Hippo kinase (Mst1) on mitochondrial damage and dysfunction in the acute phase of TTS were investigated. Isoproterenol exposure induced acute increase in biomarkers of cardiac damage and ventricular contractile dysfunction and dilation. At day 1 post-Iso, we observed extensive abnormalities in mitochondrial ultrastructure, downregulation of mitochondrial marker proteins, and mitochondrial dysfunction evidenced by lower ATP content, increased lipid droplets, higher contents of lactate, and augmented reactive oxygen species (ROS). All changes were reversed by day 7. ßAR stimulation led to activation of cardiac Hippo pathway with enhanced expression of Hippo kinase Mst1 and inhibitory YAP phosphorylation, as well as reduced nuclear YAP-TEAD1 interaction. In mice with cardiac expression of inactive mutant Mst1 gene, acute mitochondrial damage and dysfunction were mitigated. Stimulation of cardiac ßAR activates Hippo pathway that mediates mitochondrial dysfunction with energy insufficiency and enhanced ROS, promoting acute but short-term ventricular dysfunction.NEW & NOTEWORTHY Takotsubo syndrome (TTS) is featured by activation of sympatho-ß-adrenoceptor (ßAR) system leading to acute loss of ventricular contractile performance. However, the molecular mechanism remains undefined. We demonstrated, in an isoproterenol-induced murine TTS-like model, extensive mitochondrial damage, metabolic dysfunction, and downregulated mitochondrial marker proteins, changes temporarily associated with cardiac dysfunction. Mechanistically, stimulation of ßAR activated Hippo signaling pathway and genetic inactivation of Mst1 kinase ameliorated mitochondrial damage and metabolic dysfunction at the acute phase of TTS.

Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Mice with activated mTORC1 in PRs also displayed other early disease features, such as a delay in photoreceptor outer segment (POS) clearance and accumulation of lipofuscin in the retinal-pigmented epithelium (RPE) and of lipoproteins at the Bruch's membrane (BrM), as well as changes in complement accumulation. Interestingly, formation of drusen-like deposits was dependent on activation of mTORC1 in cones. Both major types of advanced AMD pathologies, including geographic atrophy (GA) and neovascular pathologies, were also seen. Finally, activated mTORC1 in PRs resulted in a threefold reduction in di-docosahexaenoic acid (DHA)-containing phospholipid species. Feeding mice a DHA-enriched diet alleviated most pathologies. The data recapitulate many aspects of the human disease, suggesting that metabolic adaptations in photoreceptors could contribute to disease progression in AMD. Identifying the changes downstream of mTORC1 that lead to advanced pathologies in mouse might present new opportunities to study the role of PRs in AMD pathogenesis.

Graphene oxide disruption of homeostasis and regeneration processes in freshwater planarian Dugesia japonica via intracellular redox deviation and apoptosis.

The aquatic system is a major sink for engineered nanomaterials released into the environment. Here, we assessed the toxicity of graphene oxide (GO) using the freshwater planarian Dugesia japonica, an invertebrate model that has been widely used for studying the effects of toxins on tissue regeneration and neuronal development. GO not only impaired the growth of normal (homeostatic) worms, but also inhibited the regeneration processes of regenerating (amputated) worms, with LC10 values of 9.86 mg/L and 9.32 mg/L for the 48-h acute toxicity test, respectively. High concentration (200 mg/L) of GO killed all the worms after 3 (regenerating) or 4 (homeostasis) days of exposure. Whole-mount in situ hybridization (WISH) and immunofluorescence analyses suggest GO impaired stem cell proliferation and differentiation, and subsequently caused cell apoptosis and oxidative DNA damage during planarian regeneration. Mechanistic analysis suggests that GO disturbed the antioxidative system (enzymatic and non-enzymatic) and energy metabolism in the planarian at both molecular and genetic levels, thus causing reactive oxygen species (ROS) over accumulation and oxidative damage, including oxidative DNA damage, loss of mitochondrial membrane integrity, lack of energy supply for cell differentiation and proliferation leading to retardance of neuron regeneration. The intrinsic oxidative potential of GO contributes to the GO-induced toxicity in planarians. These data suggest that GO in aquatic systems can cause oxidative stress and neurotoxicity in planarians. Overall, regenerated tissues are more sensitive to GO toxicity than homeostatic ones, suggesting that careful handling and appropriate decisions are needed in the application of GO to achieve healing and tissue regeneration.

Screening of rosmarinic acid from Salvia miltiorrhizae acting on the novel target TRPC1 based on the 'homology modelling-virtual screening-molecular docking-affinity assay-activity evaluation' method.

CONTEXT: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. OBJECTIVE: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae. MATERIALS AND METHODS: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. RESULTS: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 µM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. DISCUSSION AND CONCLUSIONS: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Neuroprotective effect of aldose reductase knockout in a mouse model of spinal cord injury involves NF-κB pathway.

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. Aldose reductase (AR) has recently been shown to be a key component of the innate immune response. However, the mechanisms involved in AR and innate immune response remain unclear. In this study, wild-type (WT) or AR-deficiency (KO) mice were subjected to SCI by a spinal crush injury model. AR KO mice showed better locomotor recovery and smaller injury lesion areas after spinal cord crushing compared with WT mice. Here, we first demonstrated that AR deficiency repressed the expression level of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in vitro via the activation of autophagy. AR deficiency caused 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation in LPS-induced macrophages. We also found that exogenous addition of low concentrations of 4-HNE in LPS-induced macrophages had the effect of promoting further activation of NF-κB pathway, whereas high concentrations of 4-HNE had inhibitory effects. Together, these results indicated that autophagy as a mechanism underlying AR and 4-HNE in LPS-induced macrophages.

Subcutaneous phaeohyphomycosis caused by plant pathogenic Corynespora cassiicola: A case report.

Corynespora cassiicola is a common plant pathogen responsible for leaf-spotting diseases in the tropical and subtropical areas. C. cassiicola seldom causes human infections. Here we describe a case of subcutaneous phaeohyphomycosis caused by C. cassiicola in a 76-year-old Chinese man, who presented to our hospital with a purulent discharge and painful sensation on his right leg. Skin biopsy revealed an abscess, and culture confirmed C. cassiicola to be the causative agent. The result was further identified by sequence analysis of the internal transcribed spacer region. The patient was successfully treated with systemic voriconazole and wound debridement: the lesion disappeared after 20 days.

Antiperspirant effects and mechanism investigation of Mulisan decoction in rats based on plasma metabolomics.

CONTEXT: Mulisan decoction (MLS) is a classic formula of traditional Chinese medicine for treating hyperhidrosis. The mechanism remains unclear. OBJECTIVE: To investigate the antiperspirant effect and underlying mechanisms of MLS. MATERIALS AND METHODS: Fifty rats were divided into control, model, and three doses of MLS intervention groups (n = 10). Rats except for control group were induced diseases features of the applicable scope of MLS via i.p. reserpine (0.5 mg/kg/d) for 10 days. From day 11, MLS groups were administrated orally MLS at 0.6, 3, and 15 g/kg once a day for 14 days, respectively. After the last administration, sweating was induced in all rats via s.c. pilocarpine (25 mg/kg), the right hind foot of rats was stained, and sweat point numbers were observed. Rat serum was collected to detect IL-2, IL-6, IFN-γ, and TNF-α. Rat plasma was collected for endogenous metabolite analysis via UPLC-QE-Focus-MS. RESULTS: Rats treated with MLS presented a significant decrease in sweat point numbers (13.5%), increase in body weight (13.2%), and promotion in the balance of Th1/Th2 cytokine ratio via increasing IL-2 (38.3%), IFN-γ (20.1%), and TNF-α (22.0%) and decreasing IL-6 (24.7%) compared with the model group (p < 0.05). Plasma metabolomics disclosed 15 potential biomarkers related to model rats, of which two could be significantly reversed by MLS (p < 0.05). The involved pathways were pantothenate and CoA biosynthesis, and porphyrin metabolism. CONCLUSIONS: MLS demonstrated a good antiperspirant effect and metabolism improvement. These findings inspire more clinical study validation on immune improvement and antiperspirant effect.

Resting-state connectome-based support-vector-machine predictive modeling of internet gaming disorder.

Internet gaming disorder (IGD), a worldwide mental health issue, has been widely studied using neuroimaging techniques during the last decade. Although dysfunctions in resting-state functional connectivity have been reported in IGD, mapping relationships from abnormal connectivity patterns to behavioral measures have not been fully investigated. Connectome-based predictive modeling (CPM)-a recently developed machine-learning approach-has been used to examine potential neural mechanisms in addictions and other psychiatric disorders. To identify the resting-state connections associated with IGD, we modified the CPM approach by replacing its core learning algorithm with a support vector machine. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 72 individuals with IGD and 41 healthy comparison participants. The modified CPM was conducted with respect to classification and regression. A comparison of whole-brain and network-based analyses showed that the default-mode network (DMN) is the most informative network in predicting IGD both in classification (individual identification accuracy = 78.76%) and regression (correspondence between predicted and actual psychometric scale score: r = 0.44, P < 0.001). To facilitate the characterization of the aberrant resting-state activity in the DMN, the identified networks have been mapped into a three-subsystem division of the DMN. Results suggest that individual differences in DMN function at rest could advance our understanding of IGD and variability in disorder etiology and intervention outcomes.

TaD27-B gene controls the tiller number in hexaploid wheat.

Tillering is a significant agronomic trait in wheat which shapes plant architecture and yield. Strigolactones (SLs) function in inhibiting axillary bud outgrowth. The roles of SLs in the regulation of bud outgrowth have been described in model plant species, including rice and Arabidopsis. However, the role of SLs genes in wheat remains elusive due to the size and complexity of the wheat genomes. In this study, TaD27 genes in wheat, orthologs of rice D27 encoding an enzyme involved in SLs biosynthesis, were identified. TaD27-RNAi wheat plants had more tillers, and TaD27-B-OE wheat plants had fewer tillers. Germination bioassay of Orobanche confirmed the SLs was deficient in TaD27-RNAi and excessive in TaD27-B-OE wheat plants. Moreover, application of exogenous GR24 or TIS108 could mediate the axillary bud outgrowth of TaD27-RNAi and TaD27-B-OE in the hydroponic culture, suggesting that TaD27-B plays critical roles in regulating wheat tiller number by participating in SLs biosynthesis. Unlike rice D27, plant height was not affected in the transgenic wheat plants. Transcription and gene coexpression network analysis showed that a number of genes are involved in the SLs signalling pathway and axillary bud development. Our results indicate that TaD27-B is a key factor in the regulation of tiller number in wheat.

Resveratrol promoted the M2 polarization of microglia and reduced neuroinflammation after cerebral ischemia by inhibiting miR-155.

Purpose: Neuroinflammation was demonstrated to play an important role in the brain injury induced by cerebral ischemia, which was mainly mediated by microglia. MicroRNA-155 (MiR-155) was reported to promote the M1 polarization of microglia and increase neuroinflammation. Resveratrol was identified to have the ability to promote the M2 polarization of microglia and reduce inflammation. Whether resveratrol can promote the M2 polarization of microglia and further inhibit neuroinflammation after cerebral ischemia, and its correlation with miR-155 is unclear. To clarify this, we conducted this study to explore the potential of resveratrol as an effective strategy to treat cerebral ischemia induced neuroinflammation.Materials and methods:The cerebral ischemia mouse model was first constructed by middle cerebral artery occlusion (MCAO). Then resveratrol was intraperitoneally injected at 0 h, 8 h and 18 h after cerebral ischemia. Subsequently, the relative expression of miR-155 and the signature genes of M1 and M2 microglia in injured brain were measured by RT-PCR, and the concentration of pro-inflammatory and anti-inflammatory cytokines were detected by ELISA. Further, the in vitro experiments were also conducted to explore the effect of resveratrol on the inflammation mediated by LPS activated BV2 microglia.Results: Results indicated that the relative expression of miR-155 in ischemia brain and activated BV2 microglia was elevated, while resveratrol reduced the expression of miR-155. Resveratrol promoted the M2 polarization of microglia and reduced neuroinflammation in injured brain and activated BV2 microglia.Conclusions: In conclusion, this research indicated that resveratrol promoted the M2 polarization of microglia and reduced neuroinflammation after cerebral ischemia by inhibiting miR-155.

In vivo selection with lentiviral expression of Bcl2T69A/S70A/S87A mutant in hematopoietic stem cell-transplanted mice.

Current in vivo selections for hematopoietic stem cell (HSC)-based gene therapy are drug dependent and not without risk of cytotoxicity or tumorigenesis. We developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2T69A/S70A/S87A (Bcl2AAA), which makes in vivo selection drug independent and without risk of cytotoxicity or tumorigenesis. We demonstrated in HSC-transplanted mice that Bcl2AAA facilitated efficient in vivo selection in the absence of any exogenously applied drugs under both myeloablative and non-myeloablative conditioning. In mice transplanted with retrovirally transduced sca-1-positive bone marrow cells, the marked cell level increased from 26.38% of input transduced cells to 92.61 ± 0.95% of peripheral blood cells for myeloablative transplantation or to 37.82 ± 6.35% for non-myeloablative transplantation 6 months after transplantation. Bcl2AAA did not induce tumorigenesis and does not influence hematopoiesis and the function of the reconstituted blood system. However, the high-level constitutive expression of Bcl2AAA mediated by retroviral vector induced exhaustion of the marked cells after tertiary transplantation. Fortunately, low-level constitutive expression of Bcl2AAA driven by an internal promoter in lentiviral vector could both maintain the marked cell level (24.13 ± 5.27%, 27.17 ± 5.51%, 24.33 ± 5.08%, and 22.07 ± 4.44% for primary, secondary, tertiary, and quaternary recipients) and avoid the exhaustion of the marked cells even in quaternary recipients. Importantly, the low-level constitutive expression of Bcl2AAA did not induce tumorigenesis. Thus, the in vivo selection employing the low-level constitutive expression of Bcl2AAA provides a general platform which is relevant for widespread applications of gene therapy.

Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum.

Psychobehavioral intervention is an effective treatment of Internet addiction, including Internet gaming disorder (IGD). However, the neural mechanisms underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry is a common target of psychobehavioral interventions in drug addiction, and cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the study was to investigate how the VS circuitry responds to psychobehavioral interventions in IGD. In a cross-sectional study, we examined resting-state functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did not (CBI-). All participants were scanned twice with similar time interval to assess the effects of CBI. IGD subjects showed greater resting-state functional connectivity of the VS to left inferior parietal lobule (lIPL), right inferior frontal gyrus and left middle frontal gyrus, in positive association with the severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater decrease in VS-lIPL connectivity, along with amelioration in addiction severity following the intervention. These findings demonstrated that functional connectivity between VS and lIPL, each presumably mediating gaming craving and attentional bias, may be a potential biomarker of the efficacy of psychobehavioral intervention. These results also suggested that non-invasive techniques such as transcranial magnetic or direct current stimulation targeting the VS-IPL circuitry may be used in the treatment of Internet gaming disorders.

Validation and implementation of Planova™ BioEX virus filters in the manufacture of a new liquid intravenous immunoglobulin in China.

There is a continuous need to improve the viral safety of plasma products, and we here report the development and optimization of a manufacturing-scale virus removal nanofiltration step for intravenous immunoglobulin (IVIG) using the recently introduced Planova™ BioEX filter. IVIG throughput was examined for various operating parameters: transmembrane pressure, temperature, protein concentration, and prefiltration methods. The developed procedure was based on filtering undiluted process solution (50.0 g/l IVIG) under constant transmembrane pressure filtration at 294 kPa and 25 °C following prefiltration with a 0.1 µm MILLEX VV filter. The recovery of IgG was approximately 98%, and no substantial changes in biochemical characteristics were observed before and after nanofiltration in scaled-up production. A viral clearance validation study with parvovirus under worst-case conditions performed at the National Institutes for Food and Drug Control of China (NIFDC) showed PPV logarithmic reduction value (LRV) > 4. Improved viral safety of IVIG can be assured by implementing a Planova BioEX nanofiltration step to ensure effective parvovirus clearance under conditions providing excellent protein recovery and no detectable impact on product biochemical properties. This plasma-derived IVIG product is the first to be certified for parvovirus safety by the NIFDC in China.

[Protective Effects of Genistein on Myocardial Injury in Diabetic Rats].

OBJECTIVE: To investigate the effects of genistein (Gen) on myocardial injury in diabetic rats and explore its mechanisms. METHODS: Male SD rats were randomly divided into normal (N) group, diabetic (D) group, Gen 5 mg/kg treatment (L) group and Gen 25 mg/kg treatment (H) group (n=8 for each group). Intraperitoneal injection of streptozotocin was utilized to establish type 1 diabetic rat model. After successful building models, from the fifth week, the rats in the L and H groups were daily gavaged with 5 mg/kg and 25 mg/kg Gen solution, respectively. After 4 weeks of treatment with Gen, the hemodynamic parameters and fasting blood glucose (FBG) level were measured. The morphological structure and ultrastructure of myocardium were observed using HE staining and transmission electron microscopy, respectively. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione (GSH) and Caspase-3 in myocardial tissue were measured. The levels of myocardial Bcl-2 and Bax at mRNA expression were detected using RT-PCR. The levels of myocardial thioredoxin (Trx), Trx-interacting protein (TXNIP) and apoptosis signal regulating kinase 1 (ASK1) at protein expression were detected using Western blot. RESULTS: Compared with the N group, the FBG, TNF-α, IL-1ß, IL-6, MDA and Caspase-3 levels were increased (P<0.01), while hemodynamic parameters and GSH content were decreased (P<0.01), the myocardial morphological structure and ultrastructure were damaged in the D group. The levels of Bcl-2 mRNA and Trx protein expression were significantly decreased (P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly increased (P<0.01) in the D group. Compared with the D group, in the L and H groups, there was no significant difference in [CM(155mm]FBG, the TNF-α, IL-1ß, IL-6, MDA and Caspase-3 levels were decreased (P<0.05, P<0.01), while the hemodynamic parameters and GSH content were increased (P<0.05, P<0.01); the myocardial morphological structural and ultrastructural damages were alleviated; the levels of Bcl-2 mRNA and Trx protein expression were increased (P<0.05, P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly decreased (P<0.05, P<0.01). CONCLUSION: Gen exhibits a protective effect on myocardial injury in diabetic rats, and the mechanisms may be associated with the reduction of inflammatory reaction, the regulation of Trx system expression, and the inhibition of oxidative stress and cell apoptosis.

In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy.

Adeno-associated viral (AAV) vectors have shown promise as a platform for gene therapy of neurological disorders. Achieving global gene delivery to the central nervous system (CNS) is key for development of effective therapies for many of these diseases. Here we report the isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV capsid library. Systemic injection of AAV-B1 vector in adult mice and cat resulted in widespread gene transfer throughout the CNS with transduction of multiple neuronal subpopulations. In addition, AAV-B1 transduces muscle, ß-cells, pulmonary alveoli, and retinal vasculature at high efficiency. This vector is more efficient than AAV9 for gene delivery to mouse brain, spinal cord, muscle, pancreas, and lung. Together with reduced sensitivity to neutralization by antibodies in pooled human sera, the broad transduction profile of AAV-B1 represents an important improvement over AAV9 for CNS gene therapy.