OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

BACKGROUND: The skin, a vital organ protecting against microorganisms and dehydration, undergoes structural decline with aging, leading to visible issues such as wrinkles and sagging. Reduced blood vessels exacerbate vulnerability, hindering optimal cellular function and compromising skin health. Polydioxanone (PDO) biomaterials address aging concerns but produce acidic byproducts, causing inflammation. Inorganic particles and nitric oxide (NO) play crucial roles in inhibiting inflammation and promoting skin regeneration. Stem cell-derived extracellular vesicles (EVs) contribute to intercellular communication, offering the potential to enhance cell functions. The study proposes a method to enhance PDO-based medical devices by incorporating inorganic particles and immobilizing EVs, focusing on facial rejuvenation, anti-inflammatory response, collagen formation, and angiogenesis.METHOD: PDO composites with inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) were prepared and followed by EV immobilization. Comprehensive characterization included biocompatibility, anti-inflammation, collagen formation ability, and angiogenesis ability. RESULTS: Bulk-modified PDO composites demonstrated even dispersion of inorganic particles, pH neutralization, and enhanced biocompatibility. EVs immobilized on the composite surface exhibited spherical morphology. Inflammationrelated gene expressions decreased, emphasizing anti-inflammatory effects. Collagen-related gene and protein expressions increased, showcasing collagen formation ability. In addition, angiogenic capabilities were notably improved, indicating potential for skin rejuvenation. CONCLUSION The study successfully developed and characterized PDO composites with inorganic particles and EVs, demonstrating promising attributes for medical applications. These composites exhibit biocompatibility, anti-inflammatory properties, collagen formation ability, and angiogenic potential, suggesting their utility in skin rejuvenation and tissue engineering. Further research and clinical validation are essential.

Humans ; Atrial Fibrillation ; Atrial Flutter ; Lung Transplantation/adverse effects*

Previously, most fractures have been treated through bone reduction and immobilization. With an increase in the patients’ need for an early return to their normal function, development in surgical techniques and materials have accelerated. However, delayed union or non-union of the fracture site sometimes inhibits immediate return to normal life. To enhance fracture healing, diverse materials and methods have been developed. This is a review on the current modalities of fracture healing enhancement, which aims to provide a comprehensive knowledge regarding fracture healing for researchers and health practitioners.

BACKGROUND: Depression in Parkinson's disease (dPD) is closely related to quality of life. Current studies have suggested that Pingchan Granule (PCG) might be effective for treating dPD. OBJECTIVE: This study determines the efficacy of PCG for depressive symptoms in Parkinson's disease (PD). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, randomly assigned to PCG or placebo group in a 1:1 ratio and followed for 24 weeks. MAIN OUTCOME MEASURES: The primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson's Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24. RESULTS: Eighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed. CONCLUSION: Treatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD. TRIAL REGISTRATION Chinese Clinical Trial Register: ChiCTR-INR-17011949.

BACKGROUND: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media. METHODS: To compare the cell culture condition on exosomes, human umbilical cord mesenchymal stem cells (UCMSCs) were cultured with two different media, serum containing media, 10% FBS supplemented DMEM (NM) and serum-free chemically defined media, CellCor TM CD MSC (CDM). To remove FBS-derived exosomes from UCMSC cultured with NM, the medium was replaced with FBS-free DMEM for starvation during exosome isolation. The production yield and expression levels of angiogenic and pro-inflammatory factors were compared. And, the subpopulations of exosome were classified depending on the surface properties and loaded cytokines. Finally, the wound healing and angiogenic effects have been evaluated using in vitro assays. RESULTS: The UCMSC-derived exosomes under two different cell culture media could be classified into subpopulations according to the surface composition and loaded cytokines. Especially, exosome derived from UCMSC cultured with CDM showed higher expression levels of cytokines related to regenerative bioactivities which resulted in enhanced wound healing and angiogenesis. CONCLUSION CDM has the advantages to maintain cell proliferation even during the period of exosome isolations and eliminate unknown side effects caused by serumderived exosomes. Additionally, exosomes derived from UCMSC cultured with CDM show better wound healing and angiogenic effects due to a lot of regeneration-related cytokines and less pro-inflammatory cytokines compared to with NM.

BACKGROUND: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media. METHODS: To compare the cell culture condition on exosomes, human umbilical cord mesenchymal stem cells (UCMSCs) were cultured with two different media, serum containing media, 10% FBS supplemented DMEM (NM) and serum-free chemically defined media, CellCor TM CD MSC (CDM). To remove FBS-derived exosomes from UCMSC cultured with NM, the medium was replaced with FBS-free DMEM for starvation during exosome isolation. The production yield and expression levels of angiogenic and pro-inflammatory factors were compared. And, the subpopulations of exosome were classified depending on the surface properties and loaded cytokines. Finally, the wound healing and angiogenic effects have been evaluated using in vitro assays. RESULTS: The UCMSC-derived exosomes under two different cell culture media could be classified into subpopulations according to the surface composition and loaded cytokines. Especially, exosome derived from UCMSC cultured with CDM showed higher expression levels of cytokines related to regenerative bioactivities which resulted in enhanced wound healing and angiogenesis. CONCLUSION CDM has the advantages to maintain cell proliferation even during the period of exosome isolations and eliminate unknown side effects caused by serumderived exosomes. Additionally, exosomes derived from UCMSC cultured with CDM show better wound healing and angiogenic effects due to a lot of regeneration-related cytokines and less pro-inflammatory cytokines compared to with NM.

Abstract.
N,N-Dimethyltryptamine

BACKGROUND: Sevoflurane is widely used to anesthetize children because of its rapid action with minimal irritation of the airways. However, there is a high risk of agitation after emergence from anesthesia. Strabismus surgery, in particular, can trigger agitation because patients have their eyes covered in the postoperative period. The aim of this study was to determine whether or not esmolol and lidocaine could decrease emergence agitation in children. METHODS: Eighty-four patients aged 3 to 9 years undergoing strabismus surgery were randomly assigned to a control group (saline only), a group that received intravenous lidocaine 1.5 mg/kg, and a group that received intravenous esmolol 0.5 mg/kg and lidocaine 1.5 mg/kg. Agitation was measured using the objective pain score, Cole 5-point score, and Richmond Agitation Sedation Scale score at the end of surgery, on arrival in the recovery room, and 10 and 30 min after arrival. RESULTS: The group that received the combination of esmolol and lidocaine showed lower OPS and RASS scores than the other two groups when patients awoke from anesthesia (OPS = 0 (0-4), RASS = -4 [(-5)-1]) and were transferred to the recovery room (OPS = 0 (0-8), RASS = -1 [(-5)-3]) (P < 0.05). There was no significant difference in the severity of agitation among the three groups at other time points (P > 0.05). CONCLUSIONS: When pediatric strabismus surgery is accompanied by sevoflurane anesthesia, an intravenous injection of esmolol and lidocaine could alleviate agitation until arrival in the recovery room. TRIAL REGISTRATION Clinical Research Information Service, No. KCT0002925; https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=11532.
Anesthesia ; methods ; Child ; Child, Preschool ; Double-Blind Method ; Humans ; Injections, Intravenous ; Lidocaine ; administration & dosage ; pharmacology ; Propanolamines ; administration & dosage ; pharmacology ; Sevoflurane ; therapeutic use ; Strabismus ; surgery ; Wakefulness ; drug effects

To analyse the quality of three processed products of Rhizome of Curcuma wenyujin by establishing an ultra performance liquid chromatography (UPLC) method for simultaneously determining five sesquiterpene components in three processed products of rhizome of C. wenyujin and establishing UPLC fingerprints. Component determination was achieved on Waters ACQUITY UPLC BEH C₁₈ column（2.1 mm×50 mm, 1.7 μm), with acetonitrile-water as mobile phase for gradient elution. The flow rate was 0.3 mL·min⁻¹; column temperature was 30 °C; the detection wavelength was set at 214 nm and injection volume was 1 μL. The similarity was analyzed with "Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Medica (2012.130723)", and hydrophobic cluster analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted by using simca-p14.1 software to investigate the differences in components among these three kinds of processed products. The curzerene, curdione, curcumol, germacrone, furanodiene and β-elemene showed good linearity relationship with chromatographic peak area within the ranges of 10.8-320（=0.999 9）, 10.36-259（=0.998 1）, 10.54-263.5（=0.999 3）, 30.2-755（=0.999 6）and 34.38-862（=0.999 9）mg·L⁻¹, respectively; their average recoveries were 98.75%, 98.69%, 98.63%, 99.76% and 99.57% respectively, with RSD of 2.67%, 1.47%, 1.29%, 2.54% and 0.87% respectively. The similarity of 30 batches of samples was larger than 0.9, indicating good consistency of the samples. The samples can be clearly classified into three categories for HCA, PCA and OPLS-DA pattern recognition, the differential chromatographic peak among three processed products was found respectively. The results showed that the pharmacology basis had changed obviously after processing of Rhizome of C. wenyujin, so it can provide the scientific basis for rational clinical application and establishing quality standards of three processed products of Rhizome of curcuma wenyujin.