[Application of internal carotid artery stent in glomus jugular paraganglioma surgery].

Objective:To summarize the application of internal carotid artery stent in glomus jugular paraganglioma surgery, and to provide an effective strategy for reducing the risk of internal carotid artery injury. Methods:This article reviewed the surgical cases of internal carotid artery stent implanting from 2018.06 to 2022.12, and discussed the stent placement method, treatment protocols, and perioperative management strategies. Results:A total of 5 patients underwent a comprehensive evaluation of the degree of internal carotid artery invasion using imaging techniques such as MRI, carotid CT angiography （CTA）, and digital silhouette angiography （DSA）. All patients were found to have varying degrees of internal carotid artery involvement. Stenting of the internal carotid artery was performed in all patients before surgery, and the stenting process went smoothly without any internal carotid artery injury. Three months after stenting, tumor resection or subtotal resection surgery was performed to avoid internal carotid artery injury during the surgery, and the surgical process was successfully completed. Postoperative follow-up from 4 months to 2 years showed that the internal carotid artery was patent after stent placement, with great endothelialization process and no stent-related complications. Conclusion:In patients with glomus jugular paraganglioma, when preoperative imaging shows internal carotid artery involvement, preoperative stenting is a safe and effective therapeutic strategy to reinforce the arterial wall structure, protect and maintain the integrity of the artery, and reduce the risk of vascular injury during the surgery. This article summarizes the experience of internal carotid artery stent in glomus jugular paraganglioma surgery, which provides an important reference for clinical practice.

[Research advances in the mechanism of vestibular compensation and treatment].

Unlike other sensory systems, since the vestibular system maintains the tension balance of the entire system in a"push-pull" mode, local dysfunction in the system will cause the balance of the entire system to collapse. Unilateral peripheral vestibular dysfunction will cause severe vestibular symptoms, but it can recover spontaneously within a few days to several weeks. This phenomenon is called "vestibular compensation"（VC）. Since the peripheral vestibular impact in most cases is irreversible, it is widely believed that the central mechanism plays a key role in the vestibular compensation process. Static symptom is fully compensated within a few weeks, which is in parallel with the restored balance in the resting discharge of the vestibular nucleus on both sides; the incomplete compensation of dynamic deficits takes longer and is achieved mainly through the mechanism of sensory substitution and behavioral substitution. Here we briefly reviewed the mechanism of vestibular compensation and treatment in order to provide an insight into further study and clinical treatment strategies.

Qihuang Zhuyu formula alleviates coronary microthrombosis by inhibiting PI3K/Akt/αIIbß3-mediated platelet activation.

BACKGROUND: Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. METHODS: We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. RESULTS: Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbß3 and reduced the release of von Willebrand Factor (vWF), Ca2+ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbß3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbß3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. CONCLUSION: QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

The alleviating effect of ellagic acid on DSS-induced colitis via regulating gut microbiomes and gene expression of colonic epithelial cells.

The anti-inflammatory effect of ellagic acid (EA) and its possible underlying mechanism in dextran sulfate sodium (DSS)-induced mouse chronic colonic inflammation were studied. It was observed that EA administration significantly alleviated the colonic inflammation phenotypes, including decreasing the disease activity index (DAI), enhancing the body weight loss, and improving the shortened length of the colon and pathological damage of colon tissue. Additionally, EA reshaped the constitution of the gut microbiota by elevating the ratio of Bacteroidetes along with Bacteroides and Muribaculaceae, while decreasing the proportion of Firmicutes. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) revealed that the metabolic function of the gut microbiota was also changed. Furthermore, mouse colon transcriptome analysis showed that the tight junction and peroxisome proliferator-activated receptor (PPAR) signaling pathways were activated and the expressions of related genes were upregulated after EA intervention. These results showed that EA could remodel the gut bacterial composition, change the intestinal epithelial cell gene expressions in mice, and consequently improve the colonic inflammatory symptoms.

TMEM30A is essential for hair cell polarity maintenance in postnatal mouse cochlea.

BACKGROUND: Phosphatidylserine is translocated to the inner leaflet of the phospholipid bilayer membrane by the flippase function of type IV P-tape ATPase (P4-ATPase), which is critical to maintain cellular stability and homeostasis. Transmembrane protein 30A (TMEM30A) is the ß-subunit of P4-ATPase. Loss of P4-ATPase function causes sensorineural hearing loss and visual dysfunction in human. However, the function of TMEM30A in the auditory system is unclear. METHODS: P4-ATPase subtype expression in the cochlea was detected by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) at different developmental stages. Hair cell specific TMEM30A knockout mice and wild-type littermates were used for the following functional and morphological analysis. Auditory function was evaluated by auditory brainstem response. We investigated hair cell and stereocilia morphological changes by immunofluorescence staining. Scanning electron microscopy was applied to observe the stereocilia ultrastructure. Differentially expressed transcriptomes were analyzed based on RNA-sequencing data from knockout and wild-type mouse cochleae. Differentially expressed genes were verified by qRT-PCR. RESULTS: TMEM30A and subtypes of P4-ATPase are expressed in the mouse cochlea in a temporal-dependent pattern. Deletion of TMEM30A in hair cells impaired hearing onset due to progressive hair cell loss. The disrupted kinocilia placement and irregular distribution of spectrin-α in cuticular plate indicated the hair cell planar polarity disruption in TMEM30A deletion hair cells. Hair cell degeneration begins at P7 and finishes around P14. Transcriptional analysis indicates that the focal adhesion pathway and stereocilium tip-related genes changed dramatically. Without the TMEM30A chaperone, excessive ATP8A2 accumulated in the cytoplasm, leading to overwhelming endoplasmic reticulum stress, which eventually contributed to hair cell death. CONCLUSIONS: Deletion of TMEM30A led to disrupted planar polarity and stereocilia bundles, and finally led to hair cell loss and auditory dysfunction. TMEM30A is essential for hair cell polarity maintenance and membrane homeostasis. Our study highlights a pivotal role of TMEM30A in the postnatal development of hair cells and reveals the possible mechanisms underlying P4-ATPase-related genetic hearing loss.

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling.

Objective: Cisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity. Methods: We evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line. Results: Data suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal. Significance: Salubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.

A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. METHODS: Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14-3-3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. RESULTS: NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14-3-3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. CONCLUSIONS: NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.

Generation of an integration-free induced pluripotent stem cell line (JTUi004-A) from an otosclerosis patient.

Otosclerosis is caused by abnormal bone remodeling in the middle ear, resulting in progressive hearing loss, dizziness, balance problems, and tinnitus. Previous infection, stress fractures of the bony tissue surrounding the inner ear, immune disorders, and genetic factors are believed to contribute to this disease. Currently, no effective drug treatment for otosclerosis is known. Herein, we generated an induced pluripotent stem cell line from the peripheral blood mononuclear cells of an otosclerosis patient. The cell line exhibited normal morphology, karyotype, and pluripotency marker expression. A teratoma assay revealed successful differentiation into all three germ layers.

Evaluation of ultrasound-assisted L-histidine marination on beef M. semitendinosus: Insight into meat quality and actomyosin properties.

This paper aimed to evaluate the effects of ultrasound-assisted L-histidine marination (UMH) on meat quality and actomyosin properties of beef M. semitendinosus. Our results found that UMH treatment effectively avoided excessive liquid withdrawal, and disrupted myofibril integrity by modifying the water distribution and weakening connection of actin-myosin with increased muscle pH. The ultrasound-treated sample provided more opportunity for the filtration of L-histidine to intervene the isoelectric point and conformation of muscle protein. The activated caspase-3 and changes of ATPase activity in UMH-treated meat accelerated the postmortem ageing, and L-histidine might competitively inhibit the actin-myosin binding by the imidazole group. UMH decreased the surface hydrophobicity by shielding hydrophobic area and unfolding the actomyosin structure. In addition, the increased actomyosin solubility with smaller particle size enhanced the SH content for better cross-linking of myosin tail, and formation of heat-set gelling protein structure. Therefore, UMH treatment manifested the potential to improve beef quality.

Changes of Vestibular Symptoms in Menière's Disease After Triple Semicircular Canal Occlusion: A Long-Term Follow-Up Study.

BACKGROUND: The clinical efficacy of triple semicircular canal occlusion (TSCO) and vestibular nerve resection (VNS) for patients with Ménière's disease has been unclear. OBJECTIVE: To explore changes in vestibular symptoms after TSCO and its advantages compared to the classical operation of VNS in patients with Menière's disease. METHODS: In total, 36 patients with Menière's disease performed TSCO or VNS at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China from May 2005 to July 2021, and all of them were enrolled in our study. Twelve of them underwent TSCO, 23 underwent VNS, and 1 had both treatments. We compared the demographic parameters, clinical symptoms, and selected test results between the two surgical methods. Ten patients each who underwent TSCO and VNS completed the follow-up. We collected and compared data pertaining to changes in vestibular symptoms. RESULTS: No significant difference in demographic parameters, clinical symptoms, or auditory or vestibular test results was detected between the two groups preoperatively. The TSCO group with vertigo as the main complaint experienced less residual paroxysmal dizziness after surgery than the VNS group (P = 0.020). Also, 57% of the patients in the VNS group had unsteadiness after surgery, while no such problems were reported in the TSCO group (P = 0.025). CONCLUSIONS: Our study shows that TSCO controls vertigo in most Menière's disease patients, and also has the advantage of lower rates of postoperative paroxysmal dizziness and unsteadiness than VNS. Thus, TSCO may be an effective surgery for refractory Menière's disease.

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors, but its side effects limit its application. Ototoxicity, a major adverse effect of cisplatin, causes irreversible sensorineural hearing loss. Unfortunately, there are no effective approaches to protect against this damage. Autophagy has been shown to exert beneficial effects in various diseases models. However, the role of autophagy in cisplatin-induced ototoxicity has been not well elucidated. In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was attributed to increased nuclear translocation of transcription factor EB (TFEB), and this effect could be mimicked by TFEB overexpression and inhibited by TFEB gene silencing or treatment with cyclosporin A (CsA), a calcineurin inhibitor. Taken together, our findings suggest that trehalose and autophagy play a role in protecting against cisplatin-induced ototoxicity and that pharmacological enhancement of TFEB-mediated autophagy is a potential treatment for cisplatin-induced damage in cochlear HCs and HEI-OC1 cells.

Mitigation of heterocyclic amines by phenolic compounds in allspice and perilla frutescens seed extract: The correlation between antioxidant capacities and mitigating activities.

The effect of different levels of allspice and perilla frutescens seed extract (ASE and PSE) on the formation of heterocyclic amines (HCAs) in pan-fried chicken meat patties and the bioactive components found in ASE and PSE that contribute to the mitigation of HCAs were investigated in this study. DPPH radical scavenging activity was evaluated and the results indicated that APSE (ASE + PSE) showed the highest capacity to scavenge free radicals, and the most effective inhibition of HCAs formation. Furthermore, Single and mixed phenolic compounds exhibited a positive effect in scavenging free radicals and mitigating HCAs. The radical scavenging activity and HCAs inhibition effect of single phenolic compounds were highly correlated, whereas mixed phenolic compounds exhibited poor correlation. PCA analysis indicated that phenolic compounds had the maximum inhibitory effect on IQ, followed by Norharman and harman and the minimal effect on PhIP and 7,8-DiMeIQx.

miR-135b-3p Promotes Cardiomyocyte Ferroptosis by Targeting GPX4 and Aggravates Myocardial Ischemia/Reperfusion Injury.

Ferroptosis is a form of cell death induced by excess iron and accumulation of reactive oxygen species in cells. Recently, ferroptosis has been reported to be associated with cancer and ischemia/reperfusion (I/R) injury in multiple organs. However, the regulatory effects and underlying mechanisms of myocardial I/R injury are not well-understood. The role of miR-135b-3p as an oncogene that accelerates tumor development has been confirmed; however, its role in myocardial I/R is not fully understood. In this study, we established an in vivo myocardial I/R rat model and an in vitro hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocyte injury model and observed that ferroptosis occurred in tissues and cells during I/R myocardial injury. We used database analysis to find miR-135b-3p and validated its inhibitory effect on the ferroptosis-related gene glutathione peroxidase 4 (Gpx4), using a luciferase reporter assay. Furthermore, miR-135b-3p was found to promote the myocardial I/R injury by downregulating GPX4 expression. The results of this study elucidate a novel function of miR-135b-3p in exacerbating cardiomyocyte ferroptosis, providing a new therapeutic target for improving I/R injury.

Stepwise Induction of Inner Ear Hair Cells From Mouse Embryonic Fibroblasts via Mesenchymal- to-Epithelial Transition and Formation of Otic Epithelial Cells.

Although embryonic stem cells or induced pluripotent stem cells are able to differentiate into inner ear hair cells (HCs), they have drawbacks limiting their clinical application, including a potential risk of tumourigenicity. Direct reprogramming of fibroblasts to inner ear HCs could offer an alternative solution to this problem. Here, we present a stepwise guidance protocol to induce mouse embryonic fibroblasts to differentiate into inner ear HC-like cells (HCLs) via mesenchymal-to-epithelial transition and then acquisition of otic sensory epithelial cell traits by overexpression of three key transcription factors. These induced HCLs express multiple HC-specific proteins, display protrusions reminiscent of ciliary bundle structures, respond to voltage stimulation, form functional mechanotransduction channels, and exhibit a transcriptional profile of HC signature. Together, our work provides a new method to produce functional HCLs in vitro, which may have important implications for studies of HC development, drug discovery, and cell replacement therapy for hearing loss.

Identifying genetic risk variants associated with noise-induced hearing loss based on a novel strategy for evaluating individual susceptibility.

BACKGROUND: The overall genetic profile for noise-induced hearing loss (NIHL) remains elusive. Herein we proposed a novel machine learning (ML) based strategy to evaluate individual susceptibility to NIHL and identify the underlying genetic risk variants based on a subsample of participants with extreme phenotypes. METHODS: Five features (age, sex, cumulative noise exposure [CNE], smoking, and alcohol drinking status) of 5,539 shipbuilding workers from large cross-sectional surveys were included in four ML classification models to predict their hearing levels. The area under the curve (AUC) and prediction accuracy were exploited to evaluate the performance of the models. Based on the prediction error of the ML models, the NIHL-susceptible group (n=150) and NIHL-resistant group (n=150) with a paradoxical relationship between hearing levels and features were separately screened, to identify the underlying variants associated with NIHL risk using whole-exome sequencing (WES). Subsequently, candidate risk variants were validated in an additional replication cohort (n=2108), followed by a meta-analysis. RESULTS: With 10-fold cross-validation, the performances of the four ML models were robust and similar, with average AUCs and accuracies ranging from 0.783 to 0.798 and 73.7% to 73.8%, respectively. The phenotypes of the NIHL-susceptible and NIHL-resistant groups were significantly different (all p<0.001). After WES analysis and filtering, 12 risk variants contributing to NIHL susceptibility were identified and replicated. The meta-analyses showed that the A allele of CDH23 rs41281334 (odds ratio [OR]=1.506, 95% confidence interval [CI]=1.106-2.051) and the C allele of WHRN rs12339210 (OR=3.06, 95% CI=1.398-6.700) were significantly associated with increased risk of NIHL after adjustment for confounding factors. CONCLUSIONS: This study revealed two genetic variants in CDH23 rs41281334 and WHRN rs12339210 that associated with NIHL risk, based on a promising approach for evaluating individual susceptibility using ML models.

Effects of the structure and gel properties of myofibrillar protein on chicken breast quality treated with ultrasound-assisted potassium alginate.

This paper aimed to evaluate the effects of the structure and gel properties of myofibrillar protein (MP) on 300-days-old chicken breast quality treated with ultrasound (300 W) and low addition (4 mg/mL) of potassium alginate (UPA). The results showed that UPA group exhibited lower liquid loss and optimized texture correlated with the formed water barrier and damaged myofibrils. UPA reduced the MP size and increased its solubility, and the decreased myosin thermostability and dissociated actomyosin reduced heating time for improved texture. UPA improved the gel strength, elastic modulus and ordered-arrangement of network. During gelation, the aggregation of myosin head was weakened and cross-linking of myosin tail and PA molecules was enhanced by hydrophobic interactions. UPA further inhibited the formation of disulfide bonds of myosin head and increased gel firmness. The lower myosin gelling temperature thus accelerated gel formation, and enhanced protein association with PA molecules facilitated the better gel performance.

Ultrasound-guided anterior iliopsoas muscle space block versus posterior lumbar plexus block in hip surgery in the elderly: A randomised controlled trial.

BACKGROUND: Ultrasound-guided posterior lumbar plexus block is widely used for hip fracture surgery but it requires a change of position, which may be painful. OBJECTIVES: Our primary objective was to describe a new technique, the anterior iliopsoas muscle space block, which can be performed in the supine position, and to test the hypothesis that its analgesia for hip surgery was similar to that of the traditional posterior lumbar plexus block. DESIGN: Randomised, double-blind study. SETTING: Shanghai 6th People's Hospital, China, from February to August 2019. PATIENTS: Forty-eight patients scheduled for unilateral hip fracture surgery were included in the study. The exclusion criteria were infection at the puncture site, history of hip surgery, pre-existing neurological deficits of the lower extremity, contraindications for regional anaesthesia, allergy to local anaesthetics, coagulopathy, abuse of medicine or alcohol, or daily consumption of analgesics. INTERVENTIONS: Patients were randomised to receive a lateral sacral plexus block with either an anterior iliopsoas muscle space block or a posterior lumbar plexus block, using 0.33% ropivacaine (30 ml each). MAIN OUTCOME MEASURES: The main outcome was verbal numerical scale (VNS) pain intensity 1 h after surgery in the postanesthesia care unit, and the secondary outcome was the dose of intra-operative fentanyl. The differences in VNS scores and fentanyl use between the groups were analysed. RESULTS: Based on previous work, we considered a difference (confidence interval [CI]) of 1.6 on the VNS to be significant. The median [IQR] pain scores in postanesthesia care unit were similar in the anterior 0 [0 to 3] and posterior groups 1.5 [0 to 3]. The median scores for intra-operative fentanyl use were similar in the anterior 20 [10 to 42.5] µg and posterior groups 15 [0 to 50] µg (P = 0.34). The difference in the median pain score at-rest was NS: anterior group 0.5 [0 to 5], posterior group 0 [0 to 2], median difference -0.5 (95% CI -2 to 0). The median post to preblock difference in VNS was higher in the anterior -0.5 [-2 to 0] than in the posterior group 0 [-1.25 to 0], median difference 0.5 (95% CI 0 to 1). The median block onset time was longer in the anterior 11 [6 to 14.25] min than in the posterior group 6 [4.75 to 8] min (P = 0.002), median difference -5 (95% CI -7 to -1). CONCLUSION: The anterior iliopsoas muscle space block had the same effect as the posterior lumbar plexus block on peri-operative analgesia for hip surgery, but with a longer onset time. Therefore, anterior iliopsoas muscle space block can be recommended as a routine technique for hip and lower limb procedures. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR1900021214.

Erythropoietin Plays a Protective Role in Submandibular Gland Hypofunction Induced by Irradiation.

PURPOSE: This study aims to explore the radioprotective effects of recombinant human erythropoietin (rhEPO) on rats' submandibular gland hypofunction induced by irradiation (IR). MATERIALS AND METHODS: Thirty rats were divided into 3 groups: 1) control group, 2) IR group, and 3) IR + rhEPO group. The IR group and IR + rhEPO group received a single dose of 15 Grays (Gy) (0.98 Gy/min), plus, the IR + rhEPO group also received subcutaneous administration of rhEPO at a dose of 3,000 IU/kg body weight 3 days before irradiation and then repeated every 24 hours for the first 2 weeks after irradiation. Immunohistochemistry analysis to erythropoietin receptor was performed to detect the levels of erythropoietin receptor in submandibular glands with or without radiation. Ninety days after irradiation, the salivary flow rates were assessed, and the submandibular gland of every rat was subjected to hematoxylin and eosin staining and immunohistochemical staining with antiaquaporin 5 and anti-proliferating cell nuclear antigen antibodies. Apoptosis was examined by the terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling assay. In addition, to examine the protective role of rhEPO on human submandibular gland cells, the apoptotic and proliferation rate of cells under a radiation dose of 8 Gy was detected. One-way analysis of variance was carried out to analyze the results of each group, and the P value was set at 0.05. RESULTS: Erythropoietin receptor was expressed in the submandibular glands at a low level under normal conditions but upregulated after irradiation. rhEPO administration remarkably alleviated gland atrophy, increased salivary flow rates with upregulation of aquaporin-5 compared with the IR group. In addition, fewer apoptotic cells and more proliferative cells were observed in the IR + rhEPO group compared with the IR group, both in vivo and in vitro. CONCLUSIONS: rhEPO administration may be a useful countermeasure to mitigate submandibular gland hypofunction after therapeutic radiation exposure.

Fibula osteal flap with proximal peroneal perforator skin paddle for composite oromandibular reconstruction: A case report.

RATIONALE: Cutaneous perforators of peroneal vessels are divided into proximal and distal perforators on the basis of perforator distributions and musculocutaneous or septocutaneous properties. The traditional fibular osteocutaneous free flap is raised over the distal two-thirds of the fibula with a skin paddle based on distal perforators, which is affixed to the posterior crural septum. However, the skin pedicle may not be available due to anatomic variations or intraoperative injuries. Herein, because of the absence of distal perforators, we reserved and expropriated proximal perforators originating from the musculocutaneous branch of the superior part of the peroneal artery before it divided into nutrient and arcuate arteries and successfully harvested a separate osteal fibula and proximal perforator skin paddle with a single vascular pedicle-peroneal vessel. PATIENT CONCERNS: A 62-year-old man with a 6-month history of mandibular swelling and soft tissue invasion was referred to us. DIAGNOSIS: Panoramic radiography and computed tomography showed an irregular radiolucent lesion of the mandibular body, and histopathological analysis confirmed a follicular-pattern ameloblastoma. INTERVENTIONS: The diseased mandible and soft tissue were resected and reconstructed with a vascularized fibular osteal flap with the proximal perforator skin paddle. OUTCOMES: The mandibular contour was successfully restored; the skin paddle in the mouth was in good condition after 8 months of follow-up. LESSONS: The proximal perforator is reliable and practical for supplying a skin paddle and has significant potential for future applications. We recommend reserving the proximal perforator skin paddle as a backup flap when planning to raise a fibula flap, since unavailability or injury of the traditional fibular skin island based on distal perforators occurs frequently. This approach can avoid the exploration for a second donor site, save surgical time, and reduce surgical complexity. Moreover, we anticipate more frequent use of the proximal perforator flap in the future because of its flexibility and large volume, and since it can be combined with the osteal fibula or fibular osteocutaneous flap. However, an understanding of the traits of the proximal perforator and determination of its peroneal origin by computed tomography angiography is crucial for predesigning fibular osteal flaps with a proximal perforator skin paddle.

Haploinsufficiency of Dspp Gene Causes Dentin Dysplasia Type II in Mice.

Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by heterozygous mutations in the dentin sialophosphoprotein (DSPP) gene in humans. Evidences have shown that loss of function of DSPP in Dspp knockout mice leads to phenotypes similar to DGI-III, and that the abnormal dentinogenesis is associated with decreased levels of DSPP, indicating that DSPP haploinsufficiency may play a role in dentinogenesis. Thus, to testify the haploinsufficiency of Dspp, we used a Dspp heterozygous mouse model to observe the phenotypes in the teeth and the surrounding tissues. We found that Dspp heterozygous mice displayed dentin phenotypes similar to DD-II at the ages of 12 and 18 months, which was characterized by excessive attrition of the enamel at the occlusal surfaces, thicker floor dentin of the pulp chamber, decreased pulp volume, and compromised mineralization of the dentin. In addition, the periodontium was also affected, exhibiting apical proliferation of the junctional epithelium, decreased height and width of the alveolar bone, and infiltration of the inflammatory cells, leading to the destruction of the periodontium. Both the dental and periodontal phenotypes were age-dependent, which were more severe at 18 months old than those at 12 months old. Our report is the first to claim the haploinsufficiency of Dspp gene and a DD-II mouse model, which can be further used to study the molecular mechanisms of DD-II.