Pharmacovigilance Study of Infigratinib: A Safety Analysis of the FDA Adverse Event Reporting System.

BACKGROUND: Infigratinib is a fibroblast growth factor receptor (FGFR)-specifc tyrosine kinase inhibitor indicated for the treatment of patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. However, few studies have been conducted to evaluated the safety of infigratinib in the real world. In this study, we conducted a pharmacovigilance study to evaluate the adverse events (AEs) of infigratinib by using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: OpenVigil 2.1 was employed to extract the FAERS database. Descriptive analysis was used to describe the characteristics of infigratinib-associated AE reports. Disproportionality analysis was performed by calculating the proportional reporting ratio (PRR), reporting odds ratios (ROR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals. RESULTS: Our findings revealed 149 AE reports, among which 36 significant signals were identified. These significant AE signals were mainly observed in gastrointestinal disorders (N = 26, ROR = 26.03, PRR = 8.44, information component [IC] = 3.08) and skin and subcutaneous tissue disorders (N = 21, ROR = 92.13, PRR = 40.41, IC = 5.34). Notably, dehydration and skin exfoliation were unexpected AEs, but had relatively high signal intensities (ROR = 29.75, PRR = 26.64, IC = 4.74; ROR = 50.61, PRR = 45.24, IC = 5.50, respectively) despite not being listed on the drug label. Furthermore, our analysis showed that infigratinib dose differed statistically between severe and non-severe reports (113.82 ± 16.13 mg vs 125 ± 0.00 mg, t = - 4.28; p < 0.001). However, there were no significant differences in sex, age, and types of AEs between the two groups (p  = 0.06, p  = 0.86, and p = 0.93, respectively). CONCLUSIONS: These findings suggest that gastrointestinal and skin toxicities are the most common adverse reactions for infigratinib. It is important to recognize skin exfoliation and dehydration in clinical practice, as they are unexpected AEs. Additionally, our study indicates that infigratinib dose may correlate with an increased risk of AE severity, highlighting the need for dose adjustment of infigratinib when exposure to the drug is increased due to internal or external factors.

Blood pressure variability and short-term outcomes after mechanical thrombectomy in patients with acute ischemic stroke.

OBJECTIVES: There is limited data evaluating effects of post-mechanical thrombectomy (MT) blood pressure (BP) control on short-term clinical outcomes in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). We aim to investigate the association of BP variations, after MT, with stroke early outcomes. MATERIALS AND METHODS: A retrospective study was conducted on AIS patients with LVO undergoing MT at a tertiary center over 3.5 years. Hourly BP data was recorded within the first 24- and 48-hours post-MT. BP variability was expressed as the interquartile range (IQR) of BP distribution. Short-term favorable outcome was defined as modified Rankin scale (mRS) 0-3, discharge to home or inpatient rehabilitation facility (IRF). RESULTS: Of the 95 enrolled subjects, 37(38.9%) had favorable outcomes at discharge and 8 (8.4%) died. After adjustment for confounders, an increase in IQR of systolic blood pressure (SBP) within the first 24 hours after MT revealed a significant inverse association with favorable outcomes (OR 0.43, 95% CI [0.19, 0.96], p = 0.039). Increased median MAP within the first 24 hours after MT correlated with favorable outcomes (OR 1.75, 95% CI [1.09, 2.83], p = 0.021). Subgroup analysis redemonstrated significant inverse association between increased SBP IQR and favorable outcomes (OR 0.48, 95% CI [0.21, 0.97], p = 0.042) among patients with successful revascularization. CONCLUSIONS: Post-MT high SBP variability was associated with worse short-term outcomes in AIS patients with LVO regardless of recanalization status. MAP values may be used as indicators for functional prognosis.

Modified pedicle screw fixation under guidance of stress analysis for cervicothoracic junction: Surgical technique and outcomes.

BACKGROUND: In cervicothoracic junction, the use of strong fixation device such as pedicle screw placement is often needed. OBJECTIVE: The current study aimed to evaluate the accuracy and safety of pedicle screw placement using stress conduction analysis in the clinical application. METHODS: We retrospectively collected patients who underwent pedicle screw internal fixation in cervicothoracic junction. Patients were divided into conventional nail placement (Group A) and modified pedicle screw implantation under guidance of stress analysis (Group B) according to the methods of pedicle screw placement. The accuracy of pedicle screw placement was assessed by computed tomography (CT) examination, and the success rate was calculated. RESULTS: A total of 80 patients who underwent pedicle screw internal fixation in cervicothoracic junction were included. There were no obvious differences in baseline characteristics between two groups. The success rate of total screw placement, cervical spine screw placement and upper thoracic spine screw placement in Group B was higher than those in Group A (P< 0.001, P= 0.005, P= 0.008). Additionally, Heary Grade I in the Group B was higher than Group A (P= 0.001). CONCLUSION: Stress analysis-guided technique can increase the accuracy of pedicle screw placement. Importantly, it meets the requirements of internal fixation of the cervicothoracic junction.

[Comparison of vesselplasty and percutanous kyphoplasty in the treatment of Kümmell disease].

OBJECTIVE: To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease. METHODS: The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T10 fracture, 3 cases of T12 fracture, 9 cases of L1 fractures, 5 cases of L2 fractures and 2 cases of L3 fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T10 fracture, 1 case of T11 fracture, 6 cases of T12 fracture, 10 cases of L1 fracture and 1 case of L3 fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation. RESULTS: All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison(P<0.05), and there was no statistically difference between the two groups(P>0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant(P<0.05). CONCLUSION: Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.

Reliability of shear wave elastography for the assessment of gastrocnemius fascia elasticity in healthy individual.

The mechanical properties of the deep fascia, particularly their stiffness, strongly affect the development of muscle pathologies (such as compartment syndrome) and the action of the muscles. However, the mechanical characteristics of the deep muscular fascia are still not clearly understood. The present study focuses on examining the reliability of ultrasonic shear wave elastography (USWE) devices in quantifying the shear modulus of the gastrocnemius fascia in healthy individuals, particularly their ability to measure the shear modulus of the deep fascia of the gastrocnemius during ankle dorsiflexion. Twenty-one healthy males (age: 21.48 ± 1.17 years) participated in the study. Using USWE, the shear moduli of the medial gastrocnemius fascia (MGF) and lateral gastrocnemius fascia (LGF) were quantified at different angles during passive lengthening. The two operators took turns measuring each subject's MGF and LGF over a 1-h period, and operator B took an additional measurement 2 h later. For the intra-operator test, the same subjects were measured again at the same time of day 5 days later. Both the intrarater [intraclass correlation coefficient (ICC) = 0.846-0.965)] and interrater (ICC = 0.877-0.961) reliability values for measuring the shear moduli of the MGF and LGF were rated as excellent; the standard error of the mean (SEM) was 3.49 kPa, and the minimal detectable change (MDC) was 9.68 kPa. Regardless of the ankle angle, the shear moduli of the LGF were significantly greater than that of the MGF (p < 0.001). Significant increases in the shear moduli of both the MGF and the LGF were observed in the neutral position compared to the relaxed position. These results indicate that USWE is a reliable technique to assess the shear modulus of the gastrocnemius fascia and detect its dynamic changes during ankle dorsiflexion. USWE can be used for biomechanical studies and intervention experiments concerning the deep fascia.

[Application of spinal surgical robots in minimally invasive surgery for thoracolumbar fracture].

OBJECTIVE: To evaluate the safety and accuracy of Renaissance robot navigation system in minimally invasive surgery for thoracolumbar fracture. METHODS: The clinical data of patients with thoracolumbar fracture who underwent posterior minimally invasive pedicle screw internal fixation from July 2016 to July 2019 was retrospectively analyzed. And the patients were divided into robot group and artificial group. Robot navigation assisted screw placement was used in robot group, and traditional unarmed screw placement was used in artificial group. There were 20 patients in robot group, including 13 males and 7 females, aged from 23 to 69 years old with an average of(45.05±11.81)years old, one case was T11 fracture, 2 cases were T12, 10 cases were L1, 6 cases were L2 and 1 case was L3. There were 20 patients in artificial group, including 11 males and 9 females, aged from 26 to 65 years old with an average of(43.40±11.22)years old, 2 cases were T11 fractures, 7 cases were T12, 10 cases were L1, and 1 case was L3. The numbers of fluoroscopy, operation time and intraoperative blood loss were observed. The screw position was evaluated by Neo method. RESULTS: A total of 126 screws were implanted in robot group and 124 screws were implanted in artificial group. The operation time, fluoroscopy times, intraoperative blood loss were(115.75±14.26) min, (7.95±0.89) times and (132.50±29.36) ml in robot group and (129.50±10.50) min, (14.40±2.56) times and(182.50±23.14) ml in artificial group, respectively, there was significant difference between the groups(P<0.05). According to Neo classification method, there were 122 screws at grade 0, 4 screws at grade 1 in robot group, and there were 108 screws at grade 0, 9 screws at grade 1 and 7 screws at grade 2 in artificial group. The accuracy of the robot group was better than that of artificial group(P<0.05). CONCLUSION: Compared with free hand screw placement, Renaissance robot navigation system can effectively improve the accuracy of pedicle screw placement, reduce the number of fluoroscopy times and intraoperative blood loss, thereby improving the safety of operation.

Identification of three new microsatellites and their effects on body measurement traits in pigs using time of flight-mass spectrometry (TOF-MS).

The body status of livestock affects their physiological function and productive performances. Microsatellites, one of the most used DNA markers, have been found to be associated with pig productive traits. However, their identifications and effects on body measurement traits of the Chinese Qinghai Bamei pig still uncovered. According to our previous sequencing data, in this study, three novel microsatellites were found in this breed. Using time of flight-mass spectrometry (TOF-MS) method, these microsatellites were further identified in a large Bamei pig population. TOF-MS spectra showed that there are three microsatellites loci, named P1, P2 and P3. These microsatellites were linkage equilibrium based on the values of D' and r2 tests. Association results demonstrated that P1 locus was associated with the body length, body height and chest width and the beneficial genotype was 150-/150-bp (p < 0.05); and P2 locus was associated with the body height (p < 0.05), and the 145-/145-bp, 145-/147-bp and 145-/149-bp were claimed as favorable genotypes and 145-bp allele was considered as the favorable allele. These findings suggested that P1 and P2 microsatellites might be considered as the candidate genetic markers to select pigs with superior body sizes, especially in local breed.

Elasticity of the Achilles Tendon in Individuals With and Without Plantar Fasciitis: A Shear Wave Elastography Study.

The elastic properties of the Achilles tendon (AT) are altered in local injury or other diseases and in response to changes in mechanical load. Recently, elastography has been used to evaluate variations in tendon elastic properties, mainly among healthy individuals or athletes. Therefore, this study evaluated the biomechanical changes in ATs in individuals with and without plantar fasciitis (PF). The purposes were as follows: (1) to evaluate the passive stiffness of three regions of the AT which defined as 0 (AT0 cm), 3 (AT3 cm), and 6 cm (AT6 cm) above the calcaneal tuberosity in participants with and without PF, (2) to investigate the interplay between the passive stiffness in patients with PF and pain, (3) to detect optimal cut-off points of stiffness of the AT in assessing individuals with chronic PF, and (4) to determine the correlation between the plantar fascia thickness (PFT) and pain. This cross-sectional study included 40 participants (mean age = 51 ± 13 years). When the ankle was in a relaxed position, patients with PF experienced increased passive stiffness in AT0 cm (p = 0.006) and AT3 cm (P = 0.003), but not in the neutral position. Significant correlations were observed between pain and stiffness of AT (AT0 cm r = 0.489, P = 0.029; AT3 cm r = 487, P = 0.030; AT6 cm r = 0.471, P = 0.036), but not in the PFT (P = 0.557). Optimal cut-off stiffness was AT (452 kPa) in the relaxed ankle position. The plantar fascia of patients with PF was significantly thicker than that of the controls (P < 0.001). Findings from the present study demonstrate that tendon stiffness is a good indicator of the clinical situation of patients with PF. Monitoring passive tendon stiffness may provide additional information to assess severity of the condition and guide therapeutic. The treatment programs for PF should also be tailored to the distal AT, as conventional therapy might not be targeted to tight tendons.

A novel (ATC)n microsatellite locus is associated with litter size in an indigenous Chinese pig.

Simple sequence repeats (SSRs) are an important part of the genome and have become powerful auxiliary DNA markers in animal breeding using marker-assisted selection (MAS). Based on previous sequencing data of Qinghai Bamei pigs, a total of three novel candidate SSR loci were analysed in this study. Time-of-flight mass spectrometry (TOF-MS) was used for SSR genotyping, and association analyses between SSRs and the litter size of Qinghai Bamei sows was also performed. The results of genotyping showed that the (ATC)n -P1, (AC)n -P2 and (AC)n -P3 loci had 2, 3 and 18 genotypes, respectively; 2, 3 and 8 alleles were also identified at these loci. Except for the (AC)n -P2 locus, the polymorphism information content (PIC) values of other loci were greater than 0.25. Association analyses indicated that only the (ATC)n -P1 locus was significantly associated with the litter size of Qinghai Bamei sows (p = .047). Compared to 189-/189- genotype, individuals with the 189-/195- genotype had the senior litter size, which was 9.04 ± 0.21. Our results enrich the data on SSRs in Qinghai Bamei pigs and indicate that (ATC)n -P1 is a candidate locus for MAS in the pig industry.

Micro-RNA 122 and micro-RNA 96 affected human osteosarcoma biological behavior and associated with prognosis of patients with osteosarcoma.

Osteosarcoma (OS) is the most common bone malignancy in both children and adolescents. In the present study, we aimed to explore the association of miRNA-122 and miRNA-96 expression with the clinical characteristics and prognosis of patients with osteosarcoma. The expression of miRNA-122 and miRNA-96 in human osteosarcoma cell lines and tissues were detected in the present study. Reverse transcriptase-PCR (RT-PCR) was used to determine the expression levels of miRNA-122 and miRNA-96 in 68 human OS samples. We found that MiRNA-122 and miRNA-96 were widely up-regulated in osteosarcoma, gastric cancer and pancreatic cancer. In HOS, Saos-2 and U2OS osteosarcoma cells, miRNA-122 and miRNA-96 were up-regulated significantly, while down-regulated in MG-63 cells. After further investigation, we found that miRNA-122 and miRNA-96 concentrations were significantly higher in the tumor tissues than those in the normal tissues (P<0.01). Moreover, the cell proliferation of LV-miRNA-122-RNAi and LV-miRNA-96-RNAi transfected SaOS2 was significantly decreased compared with the LV- miRNA-122-RNAi-CN and LV- miRNA-96-RNAi group. After adjusting for competing risk factors, we found combined high miRNA-122 and miRNA-96 expression was identified as independent predictor of overall survival.

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis.

Objective: Early and accurate diagnosis of multiple sclerosis (MS) remains a clinical challenge. The main objective is to evaluate the diagnostic and prognostic value of the routinely performed immunoglobulin G (IgG) index for MS patients in the Asian population. Methods: A retrospective study was conducted among a cohort of clinically isolated syndrome (CIS) patients in China with known oligoclonal band (OCB) status and IgG index at baseline. We first evaluated the predictive value of IgG index for OCB status. Secondly, the diagnostic utility and prognostic value of IgG index alone were tested. Lastly, we incorporated IgG index into the 2017 McDonald criteria by replacing OCB with either "IgG index or OCB" (modified criteria 1), "IgG index and OCB" (modified criteria 2), or "IgG index" (modified criteria 3). The diagnostic utility of different criteria was calculated and compared. Results: In a CIS cohort in China (n = 105), IgG index > 0.7 forecasted OCB positivity (X2 = 22.90, P < 0.001). An elevated IgG index was highly prognostic of more clinical relapses [1-year adjusted odds ratio [OR] = 1.32, P = 0.015; 2-years adjusted OR = 1.69, P = 0.013] and Expanded Disability Status Scale worsening (1-year adjusted OR = 1.76, P = 0.040; 2-years adjusted OR = 1.85, P = 0.032). Under the 2017 McDonald criteria (Positive Likelihood Ratio = 1.54, Negative Likelihood Ratio = 0.56), an IgG index > 0.7 in CIS patients increased the likelihood of developing MS within 2 years, either when OCB status was unknown (Positive Likelihood Ratio = 2.11) or with OCB positivity (Positive Likelihood Ratio = 2.11) at baseline; An IgG index ≤ 0.7, along with a negative OCB, helped rule out the MS diagnosis (Negative Likelihood Ratio = 0.53). Conclusions: IgG index > 0.7 predicts OCB positivity at the initial attack of MS and is prognostic of early disease activity. IgG index serves as an easily-obtainable and accurate OCB surrogate for MS diagnosis in the Asian population.

Analysis of Transcriptome and miRNAome in the Muscle of Bamei Pigs at Different Developmental Stages.

The growth of skeletal muscle involves complex developmental processes that play an important part in the determinization of pork quality. The investigation of skeletal muscle mRNA or miRNA profiles is especially important for finding molecular approaches to improve meat quality in pig breeding. Therefore, we studied the transcriptome (mRNA and miRNA) profiles of skeletal muscle with RNA-Seq in three developmental stages of pigs: 65-day embryonic (E65), postnatal 0 days (natal) and 10 months (adult). We found 10,035, 9050 and 4841 differentially expressed (DE) genes for natal vs. E65, adult vs. E65 and adult vs. natal, 55, 101 and 85 DE miRNA for natal vs. E65, adult vs. E65 and adult vs. natal, respectively. In addition, the target genes of DE miRNA that was in a negative correlation with the corresponding miRNA in the same comparison group were selected for enrichment analysis. Gene Ontology terms were mainly classified into developmental processes. Pathway analysis revealed enrichment in the Rap1 signaling pathway, citrate cycle and oxidative phosphorylation and carbon. Finally, RT-PCR was employed for validating the level of expression of 11 DE miRNA and 14 DEGs. The transcriptome profiles of skeletal muscle from the different developmental stages of the Bamei pigs were obtained. From these data, hundreds of DE miRNA and mRNA, and the miRNA-mRNA regulatory network can provide valuable insights into further understanding of key molecular mechanisms and improving the meat quality in pig breeding.

Development of ELISA and chemiluminescence enzyme immunoassay for quantification of histamine in drug products and food samples.

Histamine (HA) is a biogenic amine associated with allergies and food poisoning. It is an important indicator of food freshness and quality. In recent years, a series of medical negligence cases have been reported to be related to the intravenous injection of antibiotics produced via fermentation with fish peptone due to HA contamination. To detect HA efficiently, mouse monoclonal antibody was developed. An enzyme-linked immunosorbent assay (ELISA) and a chemiluminescence enzyme immunoassay (CLEIA) were developed and compared with conventional HPLC analysis. Both immunoassays showed low cross-reactivity, low 50% inhibitive concentration (IC50; 1.2 µg/mL and 1.1 µg/mL), low limits of detection (LODs, IC10; 89.0 ng/mL and 73.4 ng/mL), and appreciable recoveries in spiked foods and drugs (from 73.4 to 131.0% and from 77.0 to 119.0%, espectively), demonstrating that the developed methods are sensitive, specific, fast, and reliable for HA detection in complicated real samples. Graphical abstract.

Influence of different knee and ankle ranges of motion on the elasticity of triceps surae muscles, Achilles tendon, and plantar fascia.

Stiffness is a valuable indicator of the functional capabilities of muscle-tendon-fascia. Twenty healthy subjects participated in this study in which the passive elastic properties of the medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus muscles (SOL), Achilles tendon (AT, at 0 cm, 3 cm and 6 cm proximal to the calcaneus tubercle, corresponding to AT0cm, AT3cm and AT6cm, respectively) and plantar fascia (PF) were quantified when their knee was fully extended or flexed to 90° using shear wave elastography at 25° of dorsiflexion (DF25°), 0° (neutral position) of flexion, and 50° of plantar flexion (PF50°) of the ankle joint. The stiffnesses of the AT, MG, LG, SOL and the fascia with the knee fully extended were significantly higher than those with the knee flexed to 90° (p < 0.05), while the stiffness of the PF showed the opposite relationship (p < 0.05). When the knee was fully extended, the stiffness was higher in the LG than in the MG at PF50° and 0° (p < 0.01), and it was higher in the MG than in the LG at DF25° (p = 0.009). Nevertheless, regardless of the knee angle, the stiffness decreased from AT3cm > AT0cm > AT6cm at PF50° and 0° (p < 0.001), while the stiffness decreased from AT0cm > AT3cm > AT6cm at DF25°. Regardless of the knee and ankle angles, the stiffness of the PF increased in a proximal-to-distal direction (p < 0.001). These insights can be used to gain a more intuitive understanding of the relationships between the elastic properties of the muscle-tendon unit and its function.

Modulation in the elastic properties of gastrocnemius muscle heads in individuals with plantar fasciitis and its relationship with pain.

The objectives of this study were (1) to investigate the passive stiffness of the medial gastrocnemius (MG) and lateral gastrocnemius (LG) in patients with and without plantar fasciitis (PF), (2) to explore the correlation between gastrocnemius stiffness and plantar fascia thickness (PFT) as well as the intensity of pain in patients with PF, (3) to detect optimal cut-off points for stiffness of the MG and LG for identifying patients with PF. Forty patients (mean age = 51.1 years ± 12.9) participated in this study. The elastic properties of the MG and LG were quantified using shear wave elastography ultrasound. The thickness of the plantar fascia was measured by B-mode imaging. The intensity of pain was assessed using a visual analogue scale. The results showed that when the ankle was in the relaxed position, patients with PF had increased passive stiffness in the MG (P < 0.05) but not in the LG. Significant correlations were found between pain and the stiffness of the MG (middle, distal; all P-values < 0.05) and no correlation was observed between pain and PFT (P = 0.416). The initial cut-off point for the stiffness of the MG was 29.08 kPa when the ankle was in the relaxed position. The findings from the present study show that an increase in muscle stiffness is not the same in the individual muscles of the gastrocnemius muscle. Traditional treatment of the whole gastrocnemius muscle might not be targeted at the tight muscle.

Analysis of spinal stress analysis application in determining method for the pedicle screw placement under the guidance of X-Ray.

OBJECTIVE: To evaluate the accuracy of a novel guidance method of pedicle screw implantation determined by spinal stress. METHODS: We retrospectively analyzed patients underwent pedicle screw internal fixation between January 2015 and August 2018 in our hospital. Patients were divided into two groups according to the methods of pedicle screw implantation namely, the conventional nail placement and novel guidance method of pedicle screw implantation determined by spinal stress. Accuracy of spinal pedicle screw placements was evaluated using intraoperative and postoperative X-ray computed tomography (CT) examination and intraoperative touch of nerve root dissection pedicle bone. The success rate of intraoperative one-time screw placement was calculated according to Heary classification I. RESULTS: A total of 785 patients underwent pedicle screw internal fixation were retrospectively analyzed. Among them 384 patients were treated using conventional nail placement (Group A) and 401 patients were treated using the technique according to analysis of spinal stress (Group B). There was no significant difference in terms of the characteristics between two groups. There were significant differences in terms of the success rate of total of screw placement (88.7% vs. 96.2%, P < 0.001) including thoracic screw placement (87.8% vs. 94.5%, P = 0.003) and lumbar screw placement (88.8% vs. 96.5%, P = 0.001) for Group A and Group B, respectively. CONCLUSIONS: Using the novel guidance method of pedicle screw implantation determined by spinal stress might improve the accuracy of pedicle screw implantation.

Hepatic insulin resistance induced by mitochondrial oxidative stress can be ameliorated by sphingosine 1-phosphate.

The bioactive lipid mediator sphingosine 1-phosphate (S1P) is considered to be involved in the development of insulin resistance (IR) via effects on oxidative stress; the mechanism however is not yet fully revealed. To this end, we investigated the role and mechanism of S1P on hepatic IR. We found that treatment of the normal human liver cell LO2 with 1000 nM insulin for 48 h reduced glucose uptake and increased serine phosphorylation of insulin receptor substrate-1, indicating a reduction in insulin receptor signaling. Moreover, the same concentration of insulin caused accumulation of reactive oxygen species (ROS) in the cytosol and mitochondria, and enhanced expression of the antioxidant transcription factor (Nrf2) and upregulated Nrf2 nuclear translocation. Using known inhibitors and donors of ROS (H2O2, ·O2-, ·OH), the results demonstrated the differential roles for the specific ROS in regulating IR in LO2 cells, with H2O2 having a more significant inhibitory role compared with ·O2- and ·OH. Cell treatment with S1P at 0.1-5.0 µM reversed the effects of high insulin concentrations on ROS generation, glucose uptake, and insulin signaling. H2O2 also reversed the beneficial effects of S1P in alleviating IR. These results show that H2O2 signaling plays a key determinant in hepatic IR induced by insulin. S1P can ameliorate hepatic IR by reducing mitochondrial ROS generation, and the possible anti-IR effect mechanism may be involved in H2O2 signaling.

Regional Elastic Properties of the Achilles Tendon Is Heterogeneously Influenced by Individual Muscle of the Gastrocnemius.

BACKGROUND: Anatomical studies and the mechanical property studies showed that there is a strong correlation between Achilles tendon (AT) elasticity and individual gastrocnemius muscle (the medial head of gastrocnemius (MG) and the lateral head of gastrocnemius (LG)) elasticity. Limited ankle dorsiflexion range of motion has been correlated with decreased flexibility of the MG/LG/AT complex. However, no studies have been conducted to examine the exact correlation between the Achilles tendon and the individual muscle of the gastrocnemius. PURPOSES: The purposes of the present study were (1) to evaluate intra- and interoperator reliabilities of elastic property measurements in the gastrocnemius muscle-Achilles tendon complex by using the shear wave elastography (SWE) and (2) to examine the correlation between the regional elastic properties of the AT and the individual muscle of the gastrocnemius. METHODS: Twenty healthy subjects (mean age: 22.50 (3.02) years) were recruited in this study. The elastic properties of the AT and the individual muscle of the gastrocnemius were quantified using the SWE. FINDINGS: The SWE has comparatively high reliability in quantifying the elastic properties of the muscle-tendon range from good to excellent. The intraoperator ICC of the gastrocnemius muscle-Achilles tendon complex was 0.77 to 0.95, while the interoperator ICC was 0.76 to 0.94. The minimal detectable change (MDC) of the muscle was 1.72 kPa, while the AT was 32.90 kPa. A significant correlation was found between the elastic modulus of AT and the elastic modulus of the MG (r = 0.668 and p = 0.001 at the relaxing position and r = 0.481 and p = 0.032 at the neutral position). CONCLUSIONS: The SWE has the potential to assess localized changes in muscle-tendon elastic properties, provide more intuitive relations between elastic properties of the muscle tendon and function, and evaluate the therapeutic effect of the muscle tendon. A significant correlation between the AT and the MG was found, and it may provide a new treatment idea (targeted to the tight muscle heads) for the clinical setting to treat subjects with AT disorders.