A role for the cerebellum in motor-triggered alleviation of anxiety.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

Bioactivities and chemical profiling comparison and metabolomic variations of polyphenolics and steroidal glycoalkaloids in different parts of Solanum nigrum L.

INTRODUCTION: Solanum nigrum L. is a traditional medicinal herb and edible plant. Many studies provide evidence that S. nigrum L. is a nutritious vegetable. Polyphenols and steroidal glycoalkaloids are the main components. OBJECTIVES: This study aimed to systemically evaluate the phytochemical profile, quantification, and bioactivities of polyphenolics and glycoalkaloids in different parts of S. nigrum L. RESULTS: Total polyphenols (TPC) and total glycoalkaloids (TGK) were determined using the Folin-Ciocalteu and acid dye colorimetric methods, respectively. A total of 55 polyphenolic constituents (including 22 phenolic acids and 33 flavonoids) and 24 steroidal glycoalkaloids were identified from different parts using ultrahigh-performance liquid chromatography Q-exactive high-resolution mass spectrometry (UHPLC-QE-HRMS), of which 40 polyphenols (including 15 phenolic acids and 25 flavonoids) and one steroidal glycoalkaloid were characterised for the first time in S. nigrum L. Moreover, typical polyphenols and glycoalkaloids were determined using HPLC-UV and HPLC-evaporative light-scattering detector (ELSD), respectively. In addition, the TPC and TGK and their typical constituents were compared in different anatomical parts. Finally, the antioxidant capacities of polyphenolic extracts from different parts of S. nigrum L. were evaluated by ·OH, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric-reducing antioxidant power (FRAP) assay in vitro. In addition, the antitumour effects of TGK from different parts of S. nigrum L. on the proliferation of PC-3 cells were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polyphenolic and glycoalkaloid extracts from different parts of S. nigrum L. showed different antioxidant and cytotoxic capacities in vitro. CONCLUSION: This is the first study to systematically differentiate between polyphenolic and glycoalkaloid profiles from different parts of S. nigrum L.

Cerebral Hemodynamic and Metabolic Abnormalities in Neonatal Hypocalcemia: Findings from Advanced MRI.

BACKGROUND AND PURPOSE: Neonatal hypocalcemia is the most common metabolic disorder, and whether asymptomatic disease should be treated with calcium supplements remains controversial. We aimed to quantify neonatal hypocalcemia's global CBF and cerebral metabolic rate of oxygen (CMRO2) using physiologic MR imaging and elucidate the pathophysiologic vulnerabilities of neonatal hypocalcemia. MATERIALS AND METHODS: A total of 37 consecutive patients with neonatal hypocalcemia were enrolled. They were further divided into subgroups with and without structural MR imaging abnormalities, denoted as neonatal hypocalcemia-a (n = 24) and neonatal hypocalcemia-n (n = 13). Nineteen healthy neonates were enrolled as a control group. Brain physiologic parameters determined using phase-contrast MR imaging, T2-relaxation-under-spin-tagging MR imaging, and brain volume were compared between patients with neonatal hypocalcemia (their subgroups) and controls. Predictors for neonatal hypocalcemia-related brain injuries were identified using multivariate logistic regression analysis and expressed as ORs with 95% CIs. RESULTS: Patients with neonatal hypocalcemia showed significantly lower CBF and CMRO2 compared with controls. Furthermore, the neonatal hypocalcemia-a subset (versus controls or neonatal hypocalcemia-n) had significantly lower CBF and CMRO2. There was no obvious difference in CBF and CMRO2 between the neonatal hypocalcemia-n subset and controls. CBF and CMRO2 were independently associated with neonatal hypocalcemia. The ORs were 0.80 (95% CI, 0.65-0.99) and 0.97 (95% CI, 0.89-1.05) for CBF and CMRO2, respectively. CONCLUSIONS: Neonatal hypocalcemia with structural damage may exhibit lower hemodynamics and cerebral metabolism. CBF may be useful in assessing the need for calcium supplementation in asymptomatic neonatal hypocalcemia to prevent brain injury.

Multimodal quantitative magnetic resonance imaging of the thalamus in tinnitus patients with different outcomes after sound therapy.

AIMS: This study systematically investigated structural and functional alterations in the thalamus and its subregions using multimodal magnetic resonance imaging (MRI) and examined its clinical relevance in tinnitus patients with different outcomes after sound therapy (narrowband noise). METHODS: In total, 60 patients with persistent tinnitus and 57 healthy controls (HCs) were recruited. Based on treatment efficacy, 28 patients were categorized into the effective group and 32 into the ineffective group. Five MRI measurements of the thalamus and its seven subregions, including gray matter volume, fractional anisotropy, fractional amplitude of low-frequency fluctuation, and functional connectivity (FC), were obtained for each participant and compared between the groups. RESULTS: Patients in both the groups exhibited widespread functional and diffusion abnormalities in the whole thalamus and several subregions, with more obvious changes observed in the effective group. All tinnitus patients had abnormal FC compared with the HCs; FC differences between the two patient groups were only observed in the striatal network, auditory-related cortex, and the core area of the limbic system. We combined the multimodal quantitative thalamic alterations and used it as an imaging indicator to evaluate prognosis before sound therapy and achieved a sensitivity of 71.9% and a specificity of 85.7%. CONCLUSION: Similar patterns of thalamic alterations were identified in tinnitus patients with different outcomes, with more obvious changes observed in the effective group. Our findings support the tinnitus generation hypothesis of frontostriatal gating system dysfunction. A combination of multimodal quantitative thalamic properties may be used as indicators to predict tinnitus prognosis before sound therapy.

Potential herb‒drug interactions between anti-COVID-19 drugs and traditional Chinese medicine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence, hospitalization, and mortality. At present, antiviral drugs including Nirmatrelvir/Ritonavir (PaxlovidTM), Remdesivir, and Molnupiravir have been authorized to treat COVID-19 and become more globally available. On the other hand, traditional Chinese medicine (TCM) has been used for the treatment of epidemic diseases for a long history. Currently, various TCM formulae against COVID-19 such as Qingfei Paidu decoction, Xuanfei Baidu granule, Huashi Baidu granule, Jinhua Qinggan granule, Lianhua Qingwen capsule, and Xuebijing injection have been widely used in clinical practice in China, which may cause potential herb-drug interactions (HDIs) in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines. However, information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking, and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19, and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters. These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo.

Background: The florets of Carthamus tinctorius L. (Safflower) is an important traditional medicine for promoting blood circulation and removing blood stasis. However, its bioactive compounds and mechanism of action need further clarification. Objective: This study aims to investigate the effect and possible mechanism of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide (HGG) from Safflower on endothelial injury in vitro, and to verify its anti-thrombotic activity in vivo. Methods: The endothelial injury on human umbilical vein endothelial cells (HUVECs) was induced by oxygen-glucose deprivation followed by reoxygenation (OGD/R). The effect of HGG on the proliferation of HUVECs under OGD/R was evaluated by MTT, LDH release, Hoechst-33342 staining, and Annexin V-FITC apoptosis assay. RNA-seq, RT-qPCR, Enzyme-linked immunosorbent assay and Western blot experiments were performed to uncover the molecular mechanism. The anti-thrombotic effect of HGG in vivo was evaluated using phenylhydrazine (PHZ)-induced zebrafish thrombosis model. Results: HGG significantly protected OGD/R induced endothelial injury, and decreased HUVECs apoptosis by regulating expressions of hypoxia inducible factor-1 alpha (HIF-1α) and nuclear factor kappa B (NF-κB) at both transcriptome and protein levels. Moreover, HGG reversed the mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, and reduced the release of IL-6 after OGD/R. In addition, HGG exhibited protective effects against PHZ-induced zebrafish thrombosis and improved blood circulation. Conclusion: HGG regulates the expression of HIF-1α and NF-κB, protects OGD/R induced endothelial dysfunction in vitro and has anti-thrombotic activity in PHZ-induced thrombosis in vivo.

Acupuncture versus Lornoxicam in the Treatment of Acute Renal Colic: A Randomized Controlled Trial.

OBJECTIVE: To compare the analgesic efficacy and safety of acupuncture and lornoxicam in acute renal colic (ARC). DESIGN SETTING PARTICIPANT: A randomized, double-blind, parallel-controlled, single-centered trial was conducted at Susong County People's Hospital from October 2019 to November 2020. Eighty-four patients with ARC were randomly divided into lornoxicam group (Group L) and acupuncture group (Group A). Group A was treated with acupuncture at Sanyinjiao (SP6), Yinlingquan (SP9) and normal saline, and Group L was treated with sham acupuncture at SP6, SP9 and lornoxicam. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) scores and adverse reactions such as nausea and dizziness were recorded within 5, 10, 15, 20 and 40 minutes after treatment. The main outcome of this study was the short-term effective (STE) rate, the secondary outcome was the onset time, and the safety index was incidence of adverse reactions. RESULTS: A total of 80 patients completed this study, including 41 patients (21 males and 20 females) in Group L and 39 patients (21 males and 18 females) in Group A. Group A exhibited lower scores versus group L after treatment (P < 0.05). The overall STE of group L was 61.00% (25/41), significantly lower than group A [84.62% (33/39)] (P < 0.001). There was no difference in the incidence of adverse reactions between group A [2.6% (1/39)] and group L [7.3% (3/41)] (P = 0.616). The ordered logistic regression analysis showed patients receiving acupuncture therapy are more likely to be cured [OR = 2.887, 95% CI: (1.190, 7.000), P = 0.019]. CONCLUSION: Acupuncture at SP6, SP9 and intramuscular injection of lornoxicam can effectively and safely relieve ARC, but the former has faster and better analgesic effect. Moreover, the incidence of adverse reactions was similar between the two treatments. This acupuncture therapy is recommended as a complementary therapy for ARC.

Biological Functions of Diallyl Disulfide, a Garlic-Derived Natural Organic Sulfur Compound.

Garlic is widely accepted as a functional food and an excellent source of pharmacologically active ingredients. Diallyl disulfide (DADS), a major bioactive component of garlic, has several beneficial biological functions, including anti-inflammatory, antioxidant, antimicrobial, cardiovascular protective, neuroprotective, and anticancer activities. This review systematically evaluated the biological functions of DADS and discussed the underlying molecular mechanisms of these functions. We hope that this review provides guidance and insight into the current literature and enables future research and the development of DADS for intervention and treatment of multiple diseases.

Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy.

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network-level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting-state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory-related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory-related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network-level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.

Sound therapy can modulate the functional connectivity of the auditory network.

The functional connectivity of the auditory network is considered to be important in the development of tinnitus. We hypothesized that sound therapy, as a commonly used effective treatment for tinnitus, can modulate the functional connectivity of the auditory network. In this prospective observational study, we recruited 27 tinnitus patients who had undergone 12 weeks of sound therapy and 27 matched healthy controls. For the two groups of subjects, resting-state functional magnetic resonance imaging was acquired both at baseline and at the 12th week. We utilized independent component analysis and seed-based functional connectivity analysis to characterize the connectivity features of the auditory network. Interaction effects between the two groups and the two scans within the auditory network were observed, which were driven by increased functional connectivity in the left primary auditory cortex (PAC) and decreased values in the secondary auditory cortex (SAC) in tinnitus patients after treatment. Increased connections between the auditory network and limbic network, as well as decreased values with the bilateral thalami, were identified. The effects were mainly driven by the functional connectivity alterations of the SAC rather than that of the PAC. Significant positive correlations between the percent improvement in the Tinnitus Handicap Inventory (THI) score and the percentage change rates of functional connectivity between the SAC and bilateral thalami were observed. Our study contributes to the understanding of the mechanism of tinnitus and effective sound therapy, providing evidence to support the theory of a gain adaptation mechanism that quantifies the recovered gating function of the thalamus in tinnitus patients.

Outcomes at 6 months are related to brain structural and white matter microstructural reorganization in idiopathic tinnitus patients treated with sound therapy.

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6-month follow-up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3-T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel-based morphometry analysis and tract-based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory-related or nonauditory-related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.

Selenium Status in Diet Affects Acetaminophen-Induced Hepatotoxicity via Interruption of Redox Environment.

Aims: Drug-induced liver injury, especially acetaminophen (APAP)-induced liver injury, is a leading cause of liver failure worldwide. Mouse models were used to evaluate the effect of microelement selenium levels on the cellular redox environment and consequent hepatotoxicity of APAP. Results: APAP treatment affected mouse liver selenoprotein thioredoxin reductase (TrxR) activity and glutathione (GSH) level in a dose- and time-dependent manner. Decrease of mouse liver TrxR activity and glutathione level was an early event, and occurred concurrently with liver damage. The decreases in the GSH/glutathione disulfide form (GSSG) ratio and TrxR activity, and the increase of protein S-glutathionylation were correlated with the APAP-induced hepatotoxicity. Moreover, in APAP-treated mice both mild deprivation and excess supplementation with selenium increased the severity of liver injury compared with those observed in mice with normal dietary selenium levels. An increase in the oxidation state of the TrxR-mediated system, including cytosolic thioredoxin1 (Trx1) and peroxiredoxin1/2 (Prx1/2), and mitochondrial Trx2 and Prx3, was found in the livers from mice reared on selenium-deficient and excess selenium-supplemented diets upon APAP treatment. Innovation: This work demonstrates that both Trx and GSH systems are susceptible to APAP toxicity in vivo, and that the thiol-dependent redox environment is a key factor in determining the extent of APAP-induced hepatotoxicity. Dietary selenium and selenoproteins play critical roles in protecting mice against APAP overdose. Conclusion: APAP treatment in mice interrupts the function of the Trx and GSH systems, which are the main enzymatic antioxidant systems, in both the cytosol and mitochondria. Dietary selenium deficiency and excess supplementation both increase the risk of APAP-induced hepatotoxicity.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Long-Term Vegan Meditation Improved Human Gut Microbiota.

OBJECTIVE: Meditation has been widely used for the treatment of a variety of psychological, cardiovascular, and digestive diseases as well as chronic pain. Vegetarian diets can effectively prevent hypertension, metabolic diseases such as diabetes and obesity, and certain cancers. Meditation and vegetarian diets have been recognized as components of a healthy lifestyle and have therefore attracted more people around the world. Meditation can help regulate overall health through the neural-endocrine-immune network. Changes in dietary habits can affect the composition of the intestinal flora, which in turn affects human physiology, metabolism, nutrition, and immune function through the bacteria-intestine-brain axis. Here, we aimed to investigate the effect of long-term meditation and vegan diet on human intestinal flora. MATERIALS AND METHODS: The present study used 16S rDNA sequencing technology to detect the differences in intestinal flora between 12 healthy vegan subjects receiving long-term meditation training and 12 healthy omnivorous subjects who never received any meditation training. RESULTS: The results showed that, compared with the subjects in the omnivorous healthy control group who had never received any meditation training, the intestinal flora structure in the people who followed the long-term vegan meditation practices changed significantly. The intersection set between the results of the LEfSe analysis and the Wilcoxon rank sum test includes 14 bacterial genera. These 14 genera are defined as the dominant genera, and the AUC value was 0.92 in the ROC curve, which demonstrates that the 14 genera can be used as a biomarker to distinguish the two groups. Three beneficial bacteria genera (Bifidobacterium, Roseburia, and Subdoligranulum) were significantly enriched in the meditation group with a threshold of 4, according to the LDAs. The functional prediction of differentially enriched intestinal flora showed that the metabolism of tyrosine, propionate, niacin, and nicotinamide in the intestinal micro-organisms in the meditation group was significantly reduced compared with those in the control group, while the biosynthesis of flavones, flavone alcohols, butosin, and neomycin; flavonoid-mediated oocyte maturation; cytoskeleton protein pathways; and antigen processing and presentation were significantly enhanced. CONCLUSIONS: These results indicate that long-term vegan meditation plays a positive role in improving the body's immunity and adjusting endocrine and metabolic levels, enabling the body to be in a state of good health.

Programming cell pyroptosis with biomimetic nanoparticles for solid tumor immunotherapy.

Immunotherapy shows remarkable efficacy in treating several types of cancer such as melanoma, leukemia, and lung carcinoma, but its therapeutic effect for most solid tumors is still limited. Various cancer therapies, such as chemotherapy, radiotherapy and phototherapy, kill solid tumors through non-inflammatory apoptosis or ablation, rather than making solid tumors immunogenic. As a highly-inflammatory programmed cell death (PCD), pyroptosis provides a great opportunity to alleviate immunosuppression and promote a systemic immune response in treating solid tumors. Herein, by fusing breast cancer membrane onto the poly(lactic-co-glycolic acid) polymeric core, we design a biomimetic nanoparticle (BNP) loaded with indocyanine green (ICG) and decitabine (DCT) for photo-activated cancer cell pyroptosis and solid tumor immunotherapy. The tumor-homing BNP effectively accumulate in tumor with low immunogenicity. ICG in BNP puncture cancer cell membranes induces a sharp cytoplasm Ca2+ concentration increase by low-dose NIR photo-activation, which promotes cytochrome c release followed by caspase-3 activation. DCT up-regulates GSDME expression synergistically via inhibiting DNA methylation, which enhances caspase-3 cleavage to GSDME and causes cancer cell pyroptosis. Finally, photo-activated pyroptosis mediated by BNP induces an impressive systemic antitumor immunity for inhibition of both primary tumor and distant tumors. Overall, pyroptosis-associated BNP shows a novel strategy for solid tumor immunotherapy with high compatibility and wide clinical applicability.

Altered functional connectivity of the thalamus in tinnitus patients is correlated with symptom alleviation after sound therapy.

Altered functional connectivity (FC) of the thalamus has been proven to be an important finding in tinnitus patients. Tinnitus can be effectively desensitized by sound therapy. However, it is still unclear whether and how sound therapy affects the FC of the thalamus. Resting-state functional magnetic resonance imaging data and anatomical data were longitudinally collected from 25 idiopathic tinnitus patients before and after 12 weeks of sound therapy by using adjusted narrow band noise and from 25 matched healthy controls at the same time interval without any intervention. The FC of bilateral thalami were analyzed by setting the left and right thalamus as the regions of interest. Significant main effect of group on the FC of the thalamus were found mainly in the key components of the default mode network, limbic network, salience network, cognitive control network, auditory network and occipital region. FC values between the thalamus, inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC) featured higher values in the tinnitus group at baseline compared to the healthy controls and restoration in tinnitus patients after treatment. Decreased Tinnitus Handicap Inventory (THI) scores and decreased FC values between the right thalamus and right IFG were positively correlated (r = 0.476, P = 0.016). Abnormal FC of the thalamus is associated with multiple brain networks. Sound therapy has a normalizing effect on the enhanced FC of the thalamus-IFG and thalamus-ACC, representing decreased tinnitus attention control and less involvement of the noise-canceling system.

Preparation and evaluation of PEGylated asiatic acid nanostructured lipid carriers on anti-fibrosis effects.

Liver fibrosis is a major pathological feature of chronic liver diseases, and effective therapies are limited at present. Asiatic acid (AA) is a triterpenoid isolated from Centella asiatica, which exhibits efficient anti-inflammatory and anti-oxidative activities. However, AA shows very low plasma levels after oral administration. In this study, AA loading PEGylated nanostructured lipid carriers (P-AA-NLCs) were prepared. P-AA-NLCs were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction (XRD) pattern, differential scanning colorimeter (DSC), and transmission electron microscopy (TEM). The intestinal absorption, in vivo distribution, pharmacokinetics, and anti-fibrosis effects of P-AA-NLC were studied compared with that of AA-NLC. In situ single-pass intestinal perfusion model shows that there are significant differences in absorption between the free and NLCs formulation. The Peff values of P-AA-NLC were significantly enhanced in all four intestinal segments compared to AA-NLC and free AA (p < .05). fa% and Ka showed similar trends, suggesting the PEGylated NLC can improve the gastrointestinal absorption of the drug. The pharmacokinetic studies presented that P-AA-NLC prolonged blood circulation times with a 1.5-fold higher relative bioavailability compared with AA-NLC. In vivo distribution experiments demonstrated that the fluorescence concentration in the liver was higher than that in other organs and the fluorescence intensity in the liver of DIR-P-NLC was about 1.3 times that of DIR-NLC. In addition, oral administration of P-AA-NLC can significantly attenuate CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including an increase in the albumin (ALB) and decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT). Moreover, the MDA and HYP in liver tissue were downregulated, while the SOD activity was upregulated. In conclusion, P-AA-NLC can increase gastrointestinal absorption of AA and enhance anti-liver fibrosis effects in SD rats.

Analysis of the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head.

OBJECTIVE: to investigate the safety and long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head. METHOD: a total of 76 patients with non-traumatic osteonecrosis of the femoral head were admitted to our hospital from February 2012 to November 2014 and included in the study. All the patients were treated by core decompression with synthetic calcium-sulfate bone grafting. After treatment, the patients were followed-up for 12 months. The operation time, intraoperative blood loss, and perioperative complications were also recorded intraoperatively to evaluate the clinical efficacy and safety. The preoperative and postoperative pain scores measured by visual analogy score (VAS) were also recorded and compared. RESULTS: all of the 76 patients were successfully operated and included in the study. The mean operation time was 34.6±14.2 min, and the intraoperative blood loss was 23.6±8.9 mL. The patients hip functions were assessed on the basis of the Harris hip score, 3 and 12 months after operation. The excellent rates 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The imaging stabilities of the hip joints 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The patient postoperative pain scores (VAS score) gradually decreased. The VAS scores 12 months after operation were significantly lower than those before operation (P<0.05). CONCLUSION: the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head is good and accompanied with significantly improved postoperative joint functions.

Electroacupuncture for postoperative pain management after total knee arthroplasty: Protocol for a systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) is one of the most common joint replacement surgeries in the United States. Postoperative pain is still a major complication after TKA. Electroacupuncture (EA) has been commonly used in clinical practice for pain after TKA, but its effects and safety remain uncertain. This protocol is described for a systematic review to investigate the beneficial effects and safety of EA for postoperative pain after TKA. METHODS: Randomized controlled trials (RCTs) related to EA treatment of pain after TKA will be collected from 3 databases of English literature, namely PubMed, Embase, and Cochrane Library, and 4 databases of Chinese literatures, namely CBM, CNKI, VIP and Wanfang database. The retrieved trials will be those published from the time when the respective databases were built to January 2018. The therapeutic effects according to the change from baseline in the amount of pain measured by the visual analogue scale (VAS) or numerical rating scale, will be accepted as the primary outcomes. We will use RevMan V.5.3 software as well to compute the data synthesis carefully when a meta-analysis is allowed. RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis of current evidence of EA for pain after TKA. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether EA is an effective intervention for patient with postoperative pain after TKA. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42018082407.