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BACKGROUND: Analgesic tolerance due to long-term use of morphine remains a challenge for pain management. Morphine acts on µ-opioid receptors and downstream of the phosphatidylinositol 3-kinase signaling pathway to activate the mammalian target of rapamycin (mTOR) pathway. Rheb is an important regulator of growth and cell-cycle progression in the central nervous system owing to its critical role in the activation of mTOR. The hypothesis was that signaling via the GTP-binding protein Rheb in the dorsal horn of the spinal cord is involved in morphine-induced tolerance. METHODS: Male and female wild-type C57BL/6J mice or transgenic mice (6 to 8 weeks old) were injected intrathecally with saline or morphine twice daily at 12-h intervals for 5 consecutive days to establish a tolerance model. Analgesia was assessed 60 min later using the tail-flick assay. After 5 days, the spine was harvested for Western blot or immunofluorescence analysis. RESULTS: Chronic morphine administration resulted in the upregulation of spinal Rheb by 4.27 ± 0.195-fold (P = 0.0036, n = 6), in turn activating mTOR by targeting rapamycin complex 1 (mTORC1). Genetic overexpression of Rheb impaired morphine analgesia, resulting in a tail-flick latency of 4.65 ± 1.10 s (P < 0.0001, n = 7) in Rheb knock-in mice compared to 10 s in control mice (10 ± 0 s). Additionally, Rheb overexpression in spinal excitatory neurons led to mTORC1 signaling overactivation. Genetic knockout of Rheb or inhibition of mTORC1 signaling by rapamycin potentiated morphine-induced tolerance (maximum possible effect, 52.60 ± 9.56% in the morphine + rapamycin group vs. 16.60 ± 8.54% in the morphine group; P < 0.0001). Moreover, activation of endogenous adenosine 5'-monophosphate-activated protein kinase inhibited Rheb upregulation and retarded the development of morphine-dependent tolerance (maximum possible effect, 39.51 ± 7.40% in morphine + metformin group vs. 15.58 ± 5.79% in morphine group; P < 0.0001). CONCLUSIONS: This study suggests spinal Rheb as a key molecular factor for regulating mammalian target of rapamycin signaling.
Subject(s)
Monomeric GTP-Binding Proteins , Female , Male , Mice , Animals , Monomeric GTP-Binding Proteins/genetics , Monomeric GTP-Binding Proteins/metabolism , Morphine/pharmacology , Sirolimus/pharmacology , Mice, Inbred C57BL , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Pain , Mammals/metabolismABSTRACT
PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.
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PURPOSE: To explore the effectiveness of sling surgery followed by pelvic floor muscle exercises (PFME) or PFME alone for moderate stress urinary incontinence (SUI) in women and its influencing factors. METHODS: This is a prospective observational cohort study investigating whether sling surgery or PFME is preferred for pre-menopause women with moderate uncomplicated SUI. Those who received PFME alone or sling surgery were divided to PT or TVT group, respectively. The primary outcome was objective cure at 12 months. The secondary outcomes included Incontinence Impact Questionnaire-Short Form (IIQ-7) scores and PFME adherence. RESULTS: The study sample comprised 130 and 74 patients in the PT and TVT groups, respectively. There was 38.2% of patients adhered to PFME twice weekly or more often, and the compliance varied by education level. At 12 months, the objective cure rate was significantly higher in the TVT versus PT group (75.7% vs 47.7%; adjusted OR = 4.27; 95% CI, 2.05-8.87; P < 0.001). In addition, the mean reduction in IIQ-7 scores was greater in the TVT group (16.2 vs 10.0; adjusted OR = 3.38; 95% CI, 1.93-4.82; P < 0.001). However, among patients with lower education or those without adherence to PFME at 12 months, the TVT was also favorized, and the discrepancy in cure rates was greater between the two groups. CONCLUSION: Sling procedures followed by PFME demonstrate greater efficacy versus physiotherapy alone for moderate female SUI management. Continued adherence to PFME was important, even for patients undergoing sling procedures. Educational factors influenced patient PFME adherence and the advantage conferred by sling procedures.
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STATEMENT OF PROBLEM: Dynamic computer-assisted zygomatic implant surgery (dCAZIS) has been reported to provide clinical efficacy with high accuracy and low risk of complications. However, the learning curve before performing dCAZIS effectively is unknown. PURPOSE: The purpose of this in vitro study was to explore the learning curve of dCAZIS in dentists with different levels of experience in implant dentistry and navigation surgery. MATERIAL AND METHODS: Six senior dental students were randomly divided into 3 groups for initial training (FH-CI group: pretraining on freehand conventional implant surgery; FH-ZI group: pretraining on freehand ZI surgery; DN-CI group: pretraining on conventional implant surgery under dynamic navigation). Then, every operator conducted 6 repeated dCAZIS training sessions on edentulous 3-dimensional (3D) printed skull models and was asked to complete a self-report questionnaire after each training session. A total of 36 postoperative cone beam computed tomography (CBCT) scans with 144 ZI osteotomy site preparations were obtained and superimposed over the preoperative design for accuracy measurements. The operation time, 3D deviations, and results of the self-reports were recorded. Comparisons among groups were analyzed with independent-sample Kruskal-Wallis tests (α=.05), and correlations between study outcomes and the number of practices were calculated. RESULTS: Operator experience and increased practice times did not significantly affect the accuracy of dCAZIS (P>.05). However, the operation time varied among groups (P<.001), and significantly shortened with more practice, reaching 11.51 ±1.68 minutes at the fifth attempt in the FH-CI group (P<.001 compared with the first practice), 14.48 ±3.07 minutes at the third attempt in the FH-ZI group (P=.038), and 8.68 ±0.58 minutes at the sixth attempt in the DN-CI group (P<.001). All groups reached their own learning curve plateau stage within 6 practice sessions. As the number of practice sessions increased, the results from the self-report questionnaires gradually improved. CONCLUSIONS: Among dentists with different levels of experience in implant dentistry and navigation surgery, dCAZIS was found to have a learning curve with respect to operation time but not implant accuracy. Experience in ZI surgery had little impact on the learning curve of dCAZIS, but experience in navigation surgery was a key factor.
Subject(s)
Cone-Beam Computed Tomography , Learning Curve , Surgery, Computer-Assisted , Zygoma , Humans , Surgery, Computer-Assisted/methods , Zygoma/surgery , Dental Implantation, Endosseous/methods , In Vitro Techniques , Clinical Competence , Printing, Three-Dimensional , Imaging, Three-Dimensional/methodsABSTRACT
Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiolate), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785â nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.
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OBJECTIVE: We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP). METHODS: Patients with type II CSP underwent laparoscopy + bilateral uterine artery embolization (control group) or laparoscopy + BUAO (study group). Data regarding the duration of surgery, intraoperative hemorrhage, postoperative complications, the duration of the hospital stay, and the costs of hospitalization were retrospectively collected. One year later, the time to the return of the ß-human chorionic gonadotropin (ß-hCG) concentration to normal and to the return of menstruation were compared. RESULTS: The duration of surgery, time to the return of menstruation, and incidence of postoperative complications in the study group were significantly less than in the control group, but there was no significant difference in the time for ß-hCG to return to normal or the volume of intraoperative hemorrhage. The duration of hospitalization and costs for the control group were higher than those for the study group. CONCLUSION: Laparoscopy in combination with BUAO is associated with minimal trauma, rapid recovery, a short duration of surgery, low cost of hospitalization, and a low postoperative complication rate. Thus, it represents a useful new surgical treatment for type II CSP.
Subject(s)
Cesarean Section , Cicatrix , Laparoscopy , Uterine Artery Embolization , Humans , Female , Laparoscopy/methods , Laparoscopy/adverse effects , Pregnancy , Adult , Cesarean Section/adverse effects , Retrospective Studies , Uterine Artery Embolization/methods , Uterine Artery Embolization/economics , Pregnancy, Ectopic/surgery , Pregnancy, Ectopic/etiology , Uterine Artery/surgery , Postoperative Complications/etiology , Length of Stay , Treatment Outcome , Chorionic Gonadotropin, beta Subunit, Human/bloodABSTRACT
Pectic polysaccharide is a bioactive ingredient in Chrysanthemum morifolium Ramat. 'Hangbaiju' (CMH), but the high proportion of HG domain limited its use as a prebiotic. In this study, hot water, cellulase-assisted, medium-temperature alkali, and deep eutectic solvent extraction strategies were firstly used to extract pectin from CMH (CMHP). CMHP obtained by cellulase-assisted extraction had high purity and strong ability to promote the proliferation of Bacteroides and mixed probiotics. However, 4 extraction strategies led to general high proportion of HG domain in CMHPs. To further enhance the dissolution and prebiotic potential of CMHP, pectinase was used alone and combined with cellulase. The key factor for the optimal extraction was enzymolysis by cellulase and pectinase in a mass ratio of 3:1 at 1 % (w/w) dosage. The optimal CMHP had high yield (15.15 %), high content of total sugar, and Bacteroides proliferative activity superior to inulin, which was probably due to the cooperation of complex enzyme on the destruction of cell wall and pectin structural modification for raised RG-I domain (80.30 %) with relatively high degree of branching and moderate HG domain. This study provided a green strategy for extraction of RG-I enriched prebiotic pectin from plants.
Subject(s)
Bacteroides , Chrysanthemum , Pectins , Pectins/chemistry , Chrysanthemum/chemistry , Cell Proliferation/drug effects , Cellulase/chemistry , Cellulase/metabolism , Solubility , Polygalacturonase/chemistry , Polygalacturonase/metabolismABSTRACT
OBJECTIVE: To continuously absorb new teaching concepts and try new teaching methods in the process of clinical practice teaching for medical students to improve the teaching effect. METHODS: In the process of clinical practice teaching of orthopedic, the teaching concept of "hand and foot" was adopted. RESULTS: In the process of clinical practice teaching for medical students, the "hand as foot teaching philosophy" was used to explain the abstract anatomical structures, which greatly stimulated students' interest in classroom learning and achieved good teaching effects. CONCLUSION: The "hand as foot teaching philosophy" is a new teaching concept, which is worth exploring and applying in clinical practice, so as to continuously optimize and improve the theoretical system and better serve for teaching.
Subject(s)
Shoulder Dislocation , Humans , Learning , Hand , Philosophy , FootABSTRACT
Primary hyperoxaluria type 2 (PH2) is a rare hereditary disease that causes nephrolithiasis, nephrocalcinosis and kidney failure. This study aimed to investigate the clinical features and mutational spectrum of Chinese patients with PH2. A retrospective cohort study was performed on PH2 patients admitted to our center over seven years. We also systematically reviewed all the articles on Chinese PH2 patients published from January 2000 to May 2023 and conducted a meta-analysis. A total of 25 PH2 patients (10 from our center and 15 from published studies) were included in this study. The median age of onset in patients from our center was 8.50 (1.00, 24.00) years, and 50% were male. Among the full cohort of 25 Chinese patients, the median age of onset was 8.00 (0.40, 26.00) years, and 64% of them were male. Seven patients progressed to end-stage kidney disease, with a median age of 27.50 (12, 31) years. The cumulative renal survival rates were 100%, 91.67%, 45.83% and 30.56% at 10, 20, 30 and 40 years of age, respectively. A total of 18 different variants were identified, and c.864_865del was the dominant variant, accounting for 57.69% of the total alleles. Patients who were heterozygous for c.864_865del were more susceptible to nephrocalcinosis than those who were homozygous for c.864_865del and those harboring other mutations (83.33% versus 33.3% and 0%, respectively) (p = 0.025). The clinical features and mutational spectrum of Chinese PH2 patients were described. This study helps to expand awareness of the phenotypes and genotypes of Chinese PH2 patients and contributes to the improvement of diagnostic and treatment strategies for PH2 patients.
Subject(s)
Hyperoxaluria, Primary , Mutation , Humans , Hyperoxaluria, Primary/genetics , Male , Female , Retrospective Studies , Child , Adult , Adolescent , Young Adult , China/epidemiology , Child, Preschool , Asian People/genetics , Infant , Nephrocalcinosis/genetics , Nephrocalcinosis/epidemiology , Age of Onset , Kidney Failure, Chronic/genetics , East Asian People , TransaminasesABSTRACT
Introduction: Hexavalent chromium [Cr (VI)] has been identified as a human carcinogen and environmental pollutant capable of affecting multiple systems in the human body. However, the specific mechanisms by which Cr (VI) affects the human nervous system remain unclear. Objective: Following confirmation of Cr (VI)'s toxic effects on rat astrocytes, this study explores the metabolites and associated metabolic pathways of rat astrocytes under different doses of Cr (VI) exposure. Methods: Cell viability was assessed using CCK8 assays, intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescent probes, intracellular 8-hydroxydeoxyguanosine (8-OHdG) content was determined by Elisa, mitochondrial membrane potential was observed using JC-1 probes, and key metabolites were identified through untargeted metabolomics analysis. Results: With increasing Cr (VI) doses, significant decreases in cell viability were observed in the 4, 8, and 16 mg/L dose groups (p < 0.05). Elevated levels of ROS and 8-OHdG, increased caspase-3 activity, and significant reductions in mitochondrial membrane potential were observed in the 2 and 4 mg/L dose groups (p < 0.05). Untargeted metabolomics analysis revealed Cr (VI)'s impact on key metabolites such as sphingosine and methionine. Enrichment analysis of KEGG pathways highlighted the critical roles of sphingolipid metabolism and the methionine-cysteine cycle in the effects of Cr (VI) on rat astrocytes. Conclusion: Our study underscores the potential neuro-health risks associated with environmental and occupational exposure to Cr (VI) and provides new perspectives and directions for investigating neurotoxic mechanisms.
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Absorptive hypercalciuria (AH) is a prevalent cause of kidney stones, and the adenylate cyclase 10 (ADCY10) gene is a rare causative gene of AH. This study aims to investigate the genotypic and phenotypic characteristics of patients with AH caused by ADCY10 gene mutations. Whole-exome sequencing and Sanger sequencing were performed on the probands and their family members, respectively. Clinical and genetic data of patients with AH caused by ADCY10 gene mutations were collected and analysed retrospectively from the present study and published literature. Two female patients (6 years old and 1 year old) with multiple bilateral kidney stones were found to have a heterozygous c.3304T>C mutation and a heterozygous c.1726C>T mutation in the ADCY10 gene. Urinary metabolite analysis revealed that urine calcium / creatinine ratios were 0.95 mmol/mmol and 1.61 mmol/mmol, respectively. Both patients underwent thiazide intake postoperatively, and upon reexamination, urine calcium decreased to within the normal range. A total of 61 patients with AH were reported from previous and present studies. The sex ratio was 7:5 for males to females, and the mean age of onset was 23.61±20.08 years. A total of 16 ADCY10 gene mutations were identified, including seven missense (43.75%), five splicing (31.25%), two frameshift (12.50%) and two nonsense mutations (12.50%). Only two cases were identified as homozygous mutations (c.1205_1206del), and the others were heterozygous mutations. In summary, we identified two novel ADCY10 gene candidate pathogenic variants in Chinese pediatric patients, which expands the mutational spectrum of the ADCY10 gene and provides a potential diagnostic and therapeutic target.
Subject(s)
Adenylyl Cyclases , Hypercalciuria , Kidney Calculi , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Young Adult , Adenylyl Cyclases/genetics , Calcium , China , Hypercalciuria/genetics , Kidney Calculi/genetics , Retrospective StudiesABSTRACT
Triple-negative breast cancer (TNBC) is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in TNBC is affected by immunocyte infiltration in the tumor microenvironment (TME). Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism; however, its role in the TME remains unclear. In this study, we aimed to investigate the role of PGAM1 in TNBC and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in TNBC and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, significantly remodeling the TME and leading to an increase in anti-tumor immunocytes, such as CD8+ T cells and M1-macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2-macrophage, and Tregs. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti-PD-1 immunotherapy, providing a novel treatment strategy for TNBC.
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To investigate the influence of the crosslinked polyethylene (XLPE) structure on electrical performance, various analytical methods were employed to study polyethylene structures with different degrees of crosslinking. Dynamic rheological analysis was conducted to determine material shear viscosity, dynamic viscosity, storage modulus (G'), loss modulus (Gâ³), and other rheological parameters. Additionally, the electrical performance of the material was analyzed by studying the phenomenon of space charge accumulation under direct current voltage. The results indicate that with an increasing mass fraction of the crosslinking agent, the crosslink density of crosslinked polyethylene initially increases and then decreases. When the dicumyl peroxide (DCP) content exceeds 1.0 wt.%, there is an accumulation of like-polarity space charges. The best rheological processing performance of crosslinked polyethylene is observed when the DCP content is in the range of 1.0-1.5 wt.%.
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As the main saponin component of Platycodon grandiflorum A.DC, Platycodin D has been reported to have an anti-obesity effect. Due to poor oral absorption, the intestinal microflora usually transforms saponins into potential bioactive substances. In this study, we profiled the metabolic changes of platycodin D by incubating it with intestinal microflora extracted from mice feces subjected to either a standard control diet or a high-fat diet. A UPLC-LTQ-Orbitrap-MS method was used for rapid analysis of the metabolic profile of platycodin D. A total of 10 compounds were identified 9 of which were assessed to be metabolized by intestinal microflora. Dehydroxylation and deglycosylation were the major metabolic process of platycodin D. The metabolic profile of platycodin D biotransformed by intestinal microflora was elucidated based on the metabolite information. Platycodin D and its metabolites had anti-inflammatory effects in LPS-stimulated RAW 264.7 cells. Only platycodin D could alleviate lipid accumulation in FFA-treated HepG2 cells.
Subject(s)
Gastrointestinal Microbiome , Saponins , Triterpenes , Mice , Animals , Humans , Saponins/pharmacology , Saponins/metabolism , Triterpenes/pharmacology , Triterpenes/metabolism , Hep G2 CellsABSTRACT
To investigate the nucleotide variation sites (SNPs) and expression differences of the fatty acid synthase gene (FASN) in Guizhou white goats, the relationship between the variation and body size traits was investigated. In this study, DNA was extracted from the blood of 100 samples of white goats from different regions in Guizhou province, China, and the variation sites were screened using pooled sequencing by mixing DNA samples, and 242 blood samples with body size traits were used for association analysis. The allele frequency, genotype frequency, homozygosity, heterozygosity and effective gene number were calculated by using PopGene 32.0 software, the population polymorphism information content was calculated by using PIC software (Version 0.6), and the state of genetic balance of the genes was analyzed by using the chi-square test. The mRNA of FASN gene expression levels in male and female goats were investigated by using real-time fluorescence quantitative PCR (RT-qPCR). The general linear mixed model of MINTAB software (Version 16.0) was used to analyze the association between FASN gene nucleotide mutation sites and body size traits. The results showed that there was one nucleotide mutation site g.141 C/T in the target fragment of FASN gene amplification, and revealed two alleles, C and T, and three genotypes CC, CT and TT. The genotype frequencies for CC, CT and TT were 0.4308, 0.4205 and 0.1487, respectively. The allele frequencies for C and T were 0.6410 and 0.3590, respectively. The genetic homozygosity (Ho) was higher than the heterozygosity (He). The χ2 test showed that the mutation site was in the Hardy-Weinberg equilibrium state (p > 0.05). The RT-qPCR results showed that the FASN gene had different expression levels in the longissimus dorsi muscle of male and female goats, and its expression was significantly higher in male goats than in female goats. The association analysis results showed that the mutation of the FASN gene had different effects on body size traits of male and female goats, and the presence of the populations of the T allele and the TT genotype recorded higher body size traits (body weight, heart girth and wither height) in female populations. Therefore, the site of the FASN gene can be used as a candidate marker for the early selection of growth traits in Guizhou white goats.
Subject(s)
Body Size , Goats , Polymorphism, Single Nucleotide , Animals , Goats/genetics , Goats/growth & development , Female , Male , Body Size/genetics , Gene Frequency , China , GenotypeABSTRACT
BACKGROUND: By combining high-frequency and contrast-enhanced ultrasound (CEUS), the position of the severed end of a finger extensor tendon injury and the injury classification can be determined as part of a comprehensive preoperative evaluation in clinical practice. However, there have been no reports of high-frequency ultrasound combined with CEUS for the preoperative diagnosis of human finger extensor tendon injury. CASES PRESENTATION: One case of complete rupture of the extensor tendon was diagnosed by ultrasound, which was completely consistent with the surgery; one case of incomplete rupture was ultimately confirmed clinically; and one case of distal phalangeal bone base avulsion fracture with tendon contusion and missed diagnosis on the first radiographic examination was confirmed by follow-up radiographic examination. CONCLUSIONS: Different types of finger extensor tendon injuries exhibit distinctive contrast-enhanced ultrasonography findings. Combined high-frequency and contrast-enhanced ultrasound can accurately locate the position of the severed end of the finger extensor tendon injury before surgery while observing the contrast agent filling area to clarify injury classification, providing a reliable imaging basis for clinical practice and ultimately developing personalized diagnosis and treatment plans for patients to ensure minimal trauma and pain, as well as optimal treatment effects.
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BACKGROUND: Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. AIM: To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. METHODS: We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. RESULTS: The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. CONCLUSION: Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
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Promoting angiogenesis following biomaterial implantation is essential to bone tissue regeneration. Herein, the composite scaffolds composed of zein, whitlockite (WH), and levofloxacin (LEVO) were fabricated to augment bone repair by facilitating osteogenesis and angiogenesis. First, three-dimensional composite scaffolds containing zein and WH were prepared using the salt-leaching method. Then, as a model antibiotic drug, the LEVO was loaded into zein/WH scaffolds. Moreover, the addition of WH enhanced the adhesion, differentiation, and mineralization of osteoblasts. The zein/WH/LEVO composite scaffolds not only had significant osteoinductivity but also showed excellent antibacterial properties. The prepared composite scaffolds were then implanted into a calvarial defect model to evaluate their osteogenic induction effects in vivo. Micro-CT observation and histological analysis indicate that the scaffolds can accelerate bone regeneration with the contribution of endogenous cytokines. Based on amounts of data in vitro and in vivo, the scaffolds present profound effects on improving bone regeneration, especially for the favorable osteogenic, intensive angiogenic, and alleviated inflammation abilities. The results showed that the synthesized scaffolds could be a potential material for bone tissue engineering.
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OBJECTIVES: This paper evaluated the success rates of pulpotomy, compared its efficacy with non-surgical root canal treatment (NSRCT), evaluated different pulpotomy techniques, and analyzed the effectiveness of contemporary bioactive materials in managing irreversible pulpitis in mature permanent teeth. DATA SOURCES: A comprehensive literature search was conducted across multiple databases including PubMed, Web of Science, Scopus, and the Cochrane Library. Search was conducted from the inception of each database to the present, adhering to PRISMA 2020 guidelines. STUDY SELECTION: Studies were selected through a multi-step screening process, focusing on adult populations, randomized controlled trials, and single-arm trials. DATA: Fifteen randomized controlled trials and eight single-arm trials were included. For a follow-up period of more than 24 months, pooled clinical success rate of pulpotomy was 92.9 % (95 %CI;82.1-99.0 %), whereas pooled radiographic success rate was 78.5 % (95 %CI;66.7-88.4 %). Meta-analyses showed that there was no significant difference in success rates between pulpotomy and NSRCT, between full and partial pulpotomy techniques, or between Mineral Trioxide Aggregate pulpotomy and Calcium Enriched Mixture pulpotomy. The results indicated comparable efficacy across these variables. CONCLUSIONS: The study highlights the potential of less invasive treatments. Pulpotomy may be a viable alternative to NSRCT for managing irreversible pulpitis in mature permanent teeth. Limitations such as the low quality of some single-arm trials and the high risk of bias in some randomized controlled trials highlight the need for further research to standardize methodologies and broaden literature inclusion for a more comprehensive understanding of the efficacy of pulpotomy, considering the high success rates reported. Clinical Significance This quantitative systematic review recognizes the potential of full or partial pulpotomy as a viable treatment alternative to root canal therapy for managing irreversible pulpitis in mature permanent teeth. Future studies should aim for standardized protocols to validate these findings and improve patient treatment outcomes.
Subject(s)
Pulpitis , Pulpotomy , Adult , Humans , Aluminum Compounds/therapeutic use , Calcium Compounds/therapeutic use , Dentition, Permanent , Drug Combinations , Pulpitis/therapy , Pulpotomy/methods , Randomized Controlled Trials as Topic , Root Canal Filling Materials/therapeutic use , Root Canal Therapy/methods , Silicates/therapeutic use , Treatment Outcome , Controlled Clinical Trials as TopicABSTRACT
The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and communication. The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH. After 7 days consecutive morphine injection, a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4 (PDK4), phosphorylated pyruvate dehydrogenase (p-PDH) and accumulation of L-lactate was elevated in the spinal dorsal horn. Intrathecally administration of inhibitors of PDK, lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns. The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro. In this study, we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS. In this process, PDK-p-PDH-lactate axis serves a pivotal role, which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.