Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.

A 20-Year Experience with Tissue Expansion for Large Cervical Fascial Defects: An Algorithm Based on Different Clinical Flap Designs.

Over the past 20 years, we have designed various types of expanded cervical flaps for large facial defects and achieved excellent tissue matching. This study was performed to propose a treatment strategy for flap selection for the reconstruction of different facial units. The authors retrospectively reviewed the application of cervical expanded flaps for facial rehabilitation in our department between January 2003 and January 2023. The study included 122 patients with unilateral (62.3%) and bilateral (37.7%) facial deformities ranging from the zygomatic arch to the chin. The median area of the tissue defect was 15.2 × 8.5 cm2 (ranging from 6 × 4 cm2 to 27 × 12 cm2). The expansion period ranged from 61 to 175 days (mean: 86.5 days). Maximum and minimum sizes of pre-expanded cervical flaps were 30 × 13 cm2 to 7 × 5 cm2. All the flaps could be summarized into type 1, an advanced expanded cervical flap; type 2, a wing-shaped expanded cervical flap with overlapping tissue expansion; and type 3, an expanded single-lobed transposition flap rotated based on the anterior neck. Cervical flaps reliably meet the reconstructive requirements for different facial units, especially for large cutaneous defects in the clinic. The selection of these flaps can be planned preoperatively according to the location and size of the defect or lesion.

Blood Supply of the Temporal Flap Pedicled With Orbicularis Oculi Muscle: Anatomy and Its Clinical Implications.

BACKGROUND: Traumatic injury or tumor resection can lead to eyelid defects, nasal defects, and cheek defects. The temporal flap pedicled with orbicularis oculi muscle (OOM) can be used to repair these defects. This cadaver-based anatomic study aimed to evaluate the blood supply of this flap and investigate its clinical implications. METHODS: Twenty hemifaces from 10 cadavers were used in this study. The number of arteries supplying OOM of the flap, the diameter of the artery entering OOM, and the maximum width of OOM were recorded. All data were presented as mean±SD values and analyzed using Student t -test. A P value<0.05 was considered statistically significant. RESULTS: Of these 10 specimens, 7 were males and 3 were females. The average age was 67.7 years (range, 53-78 y). The number of arteries supplying OOM was 8.5±1.4 in the male and 7.8±1.2 in the female. The diameter of the zygomatico-orbital artery was detected as 0.53±0.06 mm in the male and 0.40±0.11 mm in the female. The maximum width of OOM was detected as 2.5±0.1 cm in the male and 2.2±0.1 cm in the female. Males had significantly larger average values than females in the diameter of zygomatico-orbital artery and maximum width of OOM ( P =0.012, P <0.001, respectively). However, the number of arteries supplying OOM did not differ significantly between sex ( P =0.322). CONCLUSIONS: We conclude that the blood supply of the temporal flap pedicled with OOM is abundant and reliable. The findings provide surgeons with valuable anatomic knowledge for repairing facial defects with this flap.

Using an Expanded Cervical Flap With an Overlapping Tissue Expansion Technique to Resurface Middle and Lower Facial Defects.

BACKGROUND: Extensive facial burn scars are a tragedy for patients and often pose a great challenge to surgeons because of the high esthetic and functional demands. For patients with healthy skin in the neck region, a cervical flap is highly recommended for facial resurfacing; however, the skin on the midline of the neck often needs more expansion than that on either side, especially for the treatment of large facial defects. The sufficient longitudinal soft tissue in the anterior neck ensures a normal neck shape as well as a normal range of cervical extension, rotation, and lateral flexion. To overcome this, we developed an expanded cervical flap with an overlapping tissue expansion technique to gain more length centrally. METHODS: First, 2 tissue expanders were embedded in the anterior neck region overlapping each other at the midline of the neck. After adequate inflation of the expander, the expanded flap was dissected and rotated to repair defects in the middle and lower face. The anchor position of the flap was placed on the horizontal line of the thyroid cartilage to restore the cervicomental angle. RESULTS: Sixteen patients were treated with this method in this single-center study. All defects affected the middle and lower face, with an area ranging from 135 to 185 cm 2 , and were caused by a massive facial burn. Among them, 12 patients suffered ectropion of the lower lip, 3 suffered limited mouth opening due to scar contraction, and one patient had a cervicomental adhesion. The area of the expanded flap was approximately 163 to 266 cm 2 . The average period of expansion was 89.5 days. Patients were followed up after the operation, with the follow-up period ranging from 6 to 12 months. In all cases, good defect coverage was achieved, with primary closure of the donor sites and a good postoperative cervical configuration. CONCLUSION: We conclude that the expanded cervical flap with the overlapping tissue expansion technique proved to be a reliable method for facial skin reconstruction with functional and aesthetic improvement.

Facial Defects With Infraorbital and Zygomatic Area Reconstruction Using an Expanded Flap Based on the Orbicularis Oculi Muscle: A Long-Term Follow-up.

OBJECTIVE: Reconstruction of facial soft-tissue defects may pose a dilemma for plastic surgeons, as the flaps must be reliable to obtain a natural appearance while minimizing donor site morbidities. This clinical study describes a reconstructive method for infraorbital and zygomatic defects using a pre-expanded rotation flap based on the orbicularis oculi muscle (OOM). METHODS: The surgeries were subdivided into 2 stages. In the first stage of the operation, a 100 to 200 mL expander was placed underneath the temporal area through a hairline incision. In the second stage, after adequate inflation of the expander, the pre-expanded rotation flap based on the OOM of the lower eyelid was raised from lateral to medial to cover the facial defects. RESULTS: In this single-center study from February 2010 to February 2017, 16 patients underwent facial defect reconstruction using the pre-expanded flap based on the OOM. All of the defects were located at the infraorbital and zygomatic regions, and their sizes ranged from 3.0 4.0 to 7.0 14.0 cm. The causes of these defects included postburn scars (37.5%), melanocytic nevus (50%), and hemangiomas (12.5%). In all cases, good coverage was provided for the defects that were in the medial cheek or lower eyelids. There were no flap losses of any kind. There were no major complications, and all minor incidences were treated by minimal procedures. The patients were followed up after surgery, with the follow up ranging from 6 months to 108 months. The follow-up data included postoperative consultations, the defect size, the need for further procedures and the degree of satisfaction. CONCLUSION: The pre-expanded rotation flaps in the lateral facial area based on the OOM can ideally and safely be applied for facial defect reconstruction owing to their reliable blood supply and excellent texture match.

Integrated Multi-Omics Analysis Reveals the Effect of Maternal Gestational Diabetes on Fetal Mouse Hippocampi.

Growing evidence suggests that adverse intrauterine environments could affect the long-term health of offspring. Recent evidence indicates that gestational diabetes mellitus (GDM) is associated with neurocognitive changes in offspring. However, the mechanism remains unclear. Using a GDM mouse model, we collected hippocampi, the structure critical to cognitive processes, for electron microscopy, methylome and transcriptome analyses. Reduced representation bisulfite sequencing (RRBS) and RNA-seq in the GDM fetal hippocampi showed altered methylated modification and differentially expressed genes enriched in common pathways involved in neural synapse organization and signal transmission. We further collected fetal mice brains for metabolome analysis and found that in GDM fetal brains, the metabolites displayed significant changes, in addition to directly inducing cognitive dysfunction, some of which are important to methylation status such as betaine, fumaric acid, L-methionine, succinic acid, 5-methyltetrahydrofolic acid, and S-adenosylmethionine (SAM). These results suggest that GDM affects metabolites in fetal mice brains and further affects hippocampal DNA methylation and gene regulation involved in cognition, which is a potential mechanism for the adverse neurocognitive effects of GDM in offspring.

Intrauterine Hyperglycemia Alters the Metabolomic Profile in Fetal Mouse Pancreas in a Gender-Specific Manner.

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.