The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

Pan-vascular diseases encompass a range of systemic conditions characterized by sharing a common pathologic basis of vascular deterioration. Due to the complexity of these diseases, a thorough understanding on their similarities and differences is essential for optimizing diagnosis and treatment strategies. Magnetic resonance imaging (MRI), as one of the commonly used medical imaging techniques, has been widely applied in the diagnosis of pan-vascular diseases. Particularly, the integration of MRI with contrast agents and multi-parameter imaging techniques significantly enhances diagnostic accuracy, reducing the likelihood of missed or incorrect diagnoses. Recently, a variety of nano-magnetic resonance contrast agents have been developed and applied to the magnetic resonance imaging diagnosis of diseases. These nanotechnology-based contrast agents provide multiple advantages, ensuring more precise and forward-looking imaging of pan-vascular conditions. In this review, the diverse application strategies of nanomaterials-enhanced MRI techniques in the diagnosis of pan-vascular diseases were systematically summarized, by classifying them into the commonly used MRI sequences in clinical practice. Additionally, the potential advantages and challenges associated with the clinical translation of nanomaterial-enhanced MRI were also discussed. This review not only offers a novel perspective on the precise diagnosis of pan-vascular diseases, but also serves as a valuable reference for future clinical practice and research in the field.
Humans ; Magnetic Resonance Imaging/methods* ; Contrast Media ; Vascular Diseases/diagnostic imaging* ; Nanostructures

OBJECTIVE: To investigate the analgesic effect of locally injecting a "cocktail" analgesia containing a high-dose compound betamethasone during revision hip arthroplasty, and also to study the usage of opioid drugs. METHODS: A retrospective analysis was conducted on the clinical data of 180 patients who underwent revision hip arthroplasty due to aseptic loosening of the hip prosthesis between January 2015 and December 2021. Among them, 95 patients received intraoperative injection of "cocktail" analgesia containing high-dose compound betamethasone (group A), and 85 patients received intraoperative injection of traditional "cocktail" analgesia (group B). There was no significant difference in baseline data such as gender, age, body mass index, presence or absence of diabetes mellitus between the two groups ( P>0.05). The hospital stay, use of opioid drugs within 72 hours, and the incidence of adverse reactions within 72 hours after operation [including nausea and vomiting, insomnia, deep venous thrombosis (DVT), infection, etc.] were recorded and compared between the two groups. The pain relief of patients was evaluated using the static and dynamic visual analogue scale (VAS) scores at 12, 24, 48, and 72 hours after operation. The incidence of complications (including prosthesis re-loosening, hip joint dislocation, hip joint stiffness, limping, chronic pain, etc.) at 2 years after operation was recorded, and the Harris Hip Score (HHS) was used to evaluate the function at 2 years after operation. RESULTS: In group A, the utilization rate of opioid drugs within 72 hours after operation was significantly lower than that in group B ( P<0.05). However, there was no significant difference between the two groups in terms of hospital stay, as well as the incidence of adverse reactions such as nausea and vomiting, insomnia, DVT, and infection within 72 hours after operation ( P>0.05). The VAS scores of both groups decreased with time, and the differences between different time points were significant ( P<0.05). The static and dynamic VAS scores of group A were significantly lower than those of group B at 12, 24, and 48 hours after operation ( P<0.05), but there was no significant difference in static and dynamic VAS scores between the two groups at 72 hours after operation ( P>0.05). All patients in both groups were followed up 2-8 years, with an average of 5.73 years. At 2 years after operation, no significant difference was found between the two groups in the incidence of complications and HHS score ( P>0.05). CONCLUSION "Cocktail" analgesia containing a high-dose compound betamethasone for early analgesia after revision hip arthroplasty can effectively reduce postoperative pain and the use of opioid drugs, but will not increase the incidence of infection and DVT after operation.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Betamethasone/therapeutic use* ; Retrospective Studies ; Male ; Female ; Analgesics, Opioid/administration & dosage* ; Pain, Postoperative/prevention & control* ; Middle Aged ; Reoperation ; Aged ; Analgesia/methods* ; Adult ; Pain Measurement ; Pain Management/methods* ; Prosthesis Failure ; Hip Prosthesis

OBJECTIVE: To review and summarize the research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years. METHODS: Relevant literature was reviewed to summarize the application of 3D printing technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps. RESULTS: The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps ( e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes. CONCLUSION The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with surgical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.
Printing, Three-Dimensional ; Tissue Scaffolds ; Humans ; Surgical Flaps/blood supply* ; Tissue Engineering/methods* ; Plastic Surgery Procedures/methods* ; Bone and Bones/surgery* ; Biocompatible Materials ; Bone Regeneration ; Bone Transplantation/methods* ; Bone Substitutes ; Osteogenesis

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

<p style="text-align: justify;" data-mce-style="text-align: justify;">Cough is a very common symptom causing medical consult. Several remedies are readily available in the market however these are currently not recommended among the pediatric population due to a few reasons which include the benign nature of acute cough, limited effectivity and lack of support from the United States Food and Drug Administration (USFDA) due to abuse potential.p><p style="text-align: justify;" data-mce-style="text-align: justify;">
p><p style="text-align: justify;" data-mce-style="text-align: justify;">We report a case of a 2-year-old male, no known co-morbidities with a 2 week history of upper respiratory tract infection. Initial assessment showed viral infection hence patient was given medications for symptomatic treatment. However, l week after, patient still presented with symptomatic persistent coughing that disrupted his activities of daily living, hence antitussive medication was already prescribed. After another 7 days, there was still persistence of symptoms, hence patient was given a trial medication of Pregabalin 0.7 milligram/kg/dose which noted instant cough relief one hour after the initial intake. Patient also reported to be more playful, improved sleep at night and improved appetite. Patient received total of 2 doses of Pregabalin in the span of 48 hours. On the third day, patient was still coughing but reported to be significantly less frequent and more productive, hence medication was then put on hold. Patient continuously improved after 5 more days and was eventually cough free.p><p style="text-align: justify;" data-mce-style="text-align: justify;">
p><p style="text-align: justify;" data-mce-style="text-align: justify;">This case report demonstrates the adequacy of Pregabalin as a supportive antitussive medication in a patient with an acute cough secondary to a viral infection.p>
Human ; Male ; Child Preschool: 2-5 Yrs Old ; Cough ; Pregabalin ; Respiratory System ; Respiratory Tract Infections ; Virus Diseases ; Antitussive Agents

INTRODUCTION: Postoperative urinary retention (POUR) frequently complicates the course of patients following hip and knee arthroplasty. Intrathecal morphine (ITM) was identified as a significant risk factor for POUR. The objective of this study was to investigate the incidence and risk factors for POUR in fast-track total joint arthroplasty (TJA) under spinal anaesthesia (SA) with ITM. METHODS: We conducted a retrospective study of our institutional joint registry of patients who underwent primary TJA under SA with ITM between October 2017 and May 2021. Preoperative (baseline demographics) and perioperative data were collected. The primary outcome was the incidence of POUR after 8 h or earlier, either due to lack of voiding or according to patient's complaints of bladder distension. Univariate and adjusted analyses were performed to identify predictors of POUR. RESULTS: Sixty-nine patients who underwent total knee arthroplasty (TKA) and 36 patients who underwent total hip arthroplasty (THA) under SA with ITM were included in the study. POUR requiring bladder catheterisation was diagnosed in 21% of patients. Independent predictors of POUR were age over 65 years and male gender. CONCLUSIONS SA with ITM for TJA is associated with high rates of POUR in males older than 65 years of age. Other previously identified risk factors such as intraoperative fluid administration or comorbidities may not be as influential.
Humans ; Retrospective Studies ; Male ; Urinary Retention/epidemiology* ; Arthroplasty, Replacement, Knee/adverse effects* ; Anesthesia, Spinal/adverse effects* ; Female ; Arthroplasty, Replacement, Hip/adverse effects* ; Morphine/adverse effects* ; Aged ; Middle Aged ; Risk Factors ; Postoperative Complications/epidemiology* ; Injections, Spinal ; Incidence ; Analgesics, Opioid/adverse effects* ; Aged, 80 and over

OBJECTIVE: To observe the effects of Tiaoshu Anshen (regulating the hinge and calming the mind) acupuncture on sleep quality and serum levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in patients with chronic insomnia. METHODS: A total of 58 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 29 cases in each group. Tiaoshu Anshen acupuncture was applied at Baihui (GV20) and bilateral Shenmen (HT7), Sanyinjiao (SP6), Benshen (GB13) in the acupuncture group, once a day, 1-day interval was taken after 6 consecutive days of treatment. Estazolam tablet was given orally before bed in the medication group, 1 mg each time. The 4-week treatment was required in both groups. Before and after treatment, the sleep quality was assessed by Pittsburgh sleep quality index (PSQI) and polysomnography (PSG), the serum levels of 5-HT and DA were detected by ELISA. RESULTS: After treatment, the item scores and total scores of PSQI were decreased compared with those before treatment in the two groups (P<0.05); in the acupuncture group, the scores of sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorders and total score of PSQI were lower than those in the medication group (P<0.05). After treatment, the total sleep time (TST) was prolonged (P<0.05), the sleep latency (SL) and wake after sleep onset (WASO) were shortened (P<0.05), the sleep efficiency (SE%), percentage of non-rapid eye movement stage 3 (N3%), percentage of rapid eye movement stage (REM%) and serum levels of 5-HT were increased (P<0.05) compared with those before treatment; the percentage of non-rapid eye movement stage 1 (N1%), percentage of non-rapid eye movement stage 2 (N2%) and serum levels of DA were decreased (P<0.05) compared with those before treatment in the two groups. After treatment, in the acupuncture group, TST was longer, while SL and WASO were shorter than those in the medication group (P<0.05), SE%, N3%, REM% and serum level of 5-HT were higher, while N1%, N2% and serum level of DA were lower than those in the medication group (P<0.05). CONCLUSION Tiaoshu Anshen acupuncture may improve the sleep quality by regulating the serum neurotransmitter levels i.e. 5-HT and DA in patients with chronic insomnia.
Humans ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Serotonin/blood* ; Sleep Quality ; Acupuncture Points ; Dopamine/blood* ; Aged ; Neurotransmitter Agents/blood* ; Young Adult

OBJECTIVE: To observe the regulatory effects of moxibustion at "Guanyuan" (CV4) on the synthesis of extragonadal estradiol (E₂) and the expression of estrogen receptor (ER) in ovariectomized rats, aiming to explore the mechanism of moxibustion treatment for perimenopausal syndrome. METHODS: Forty-eight SD female rats of SPF grade were randomly divided into a sham-operation group, a model group and a moxibustion group, with 16 rats in each group. The model group and the moxibustion group underwent bilateral ovariectomy by the back incision method. Ten days after surgery, moxibustion was applied at "Guanyuan" (CV4) in the moxibustion group, 30 min each time, once a day for 10 days. After intervention, in the 3 groups, the body mass and uterus weight were measured; the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and E₂, as well as the skin and hypothalamus levels of E₂ were detected by ELISA; the mRNA expression of aromatase (P450arom) in the skin and hypothalamus was detected by real-time PCR; the expression of ERα and ERβ in the hypothalamus, skin, and uterus was observed by immunofluorescence staining, and the density of positive cells was calculated using the Aipathwell digital pathology image analysis software. RESULTS: Compared with the sham-operation group, the body mass was increased (P<0.01) and the uterus weight was decreased (P<0.001) in the model group. Compared with the model group, the body mass was decreased in the moxibustion group (P<0.01). Compared with the sham-operation group, in the model group, the serum, hypothalamus and skin levels of E₂ were decreased (P<0.01, P<0.05), while the serum levels of FSH and LH were increased (P<0.01); the expression of ERα and ERβ in the skin, hypothalamus and uterus was decreased (P<0.05, P<0.001). Compared with the model group, in the moxibustion group, the serum levels of E₂ and LH, as well as the hypothalamus and skin levels of E₂ were increased (P<0.05, P<0.01); the mRNA expression of P450arom, as well as the expression of ERα and ERβ in the skin and hypothalamus were increased (P<0.05). CONCLUSION Moxibustion at "Guanyuan" (CV4) reduces the body mass of ovariectomized rats by enhancing the synthesis of extragonadal E₂ and increasing the expression of ER in the skin and hypothalamus, yet it does not alleviate uterine atrophy.
Animals ; Female ; Moxibustion ; Rats ; Ovariectomy ; Acupuncture Points ; Rats, Sprague-Dawley ; Humans ; Receptors, Estrogen/genetics* ; Estrogens/metabolism* ; Estradiol/metabolism* ; Hypothalamus/metabolism* ; Follicle Stimulating Hormone/blood* ; Aromatase/genetics* ; Luteinizing Hormone/blood* ; Skin/metabolism*