A Single-Institution Review of the Use of Radiation in the Adjuvant and Definitive Management of Keloids.

AIMS: Many individuals suffer from keloids that are refractory to standard treatment modalities, including surgical excision alone. Radiation therapy can be used to reduce the risk of recurrent keloids post-operatively, as well as be used as primary treatment for keloids not amenable to surgical resection. The purpose of this study was to review our institutional experience of radiation therapy for keloid management. MATERIALS AND METHODS: A retrospective review of patients treated with radiation therapy for keloids between 2014 and 2020 at our institution was performed. RESULTS: A total of 70 keloids in 41 patients were treated. For the 55 keloids treated with post-operative radiation therapy (16Gy delivered in 2 fractions), 82.5% (33/40) of evaluable lesions did not recur. Among the 15 keloids treated with definitive radiation therapy (24Gy delivered in 3 fractions), 78.6% (11/14) of evaluable keloids showed complete flattening, and 14.3% (2/14) had partial flattening. Both acute and late toxicities were mild, with only a single instance of grade 3 toxicity (dermatitis). CONCLUSION: Our study confirms that radiation therapy has a role in reducing the risk of keloid recurrence post-operatively, and plays an important role in the definitive management of unresectable keloids.

[Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia].

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Reduced prescription of TNF-inhibitors in chronic arthritis based on therapeutic drug monitoring: A randomized controlled trial.

OBJECTIVE: Dosing of tumour necrosis factor-α inhibitors (TNFis) is not personalized causing interindividual variation in serum drug levels; however, dose optimization is not widely implemented. We hypothesized that some patients are overdosed; thus, drug prescription could be reduced by therapeutic drug monitoring (TDM). METHOD: Independent of disease activity, 239 adults treated for rheumatoid arthritis (n = 99), psoriatic arthritis 15 (n = 48), or spondyloarthritis (n = 92) were recruited for a 48-week prospective, randomized open-label trial. Standard care alone or plus TDM was applied in chronic arthritis patients treated with infliximab (IFX), (n = 81), etanercept (ETN) (n = 79), or adalimumab (ADA) (n = 79). Serum TNFi trough levels assessed at inclusion and every 4 months determined patients within/outside predefined therapeutic intervals, supporting change in prescription or drug switch. The primary endpoint was reduced drug prescription. RESULTS: Compared to standard care, TDM reduced prescribed IFX [-12% (95% confidence interval -20, -3); p = 0.001] and ETN (-15% (-29, 1); p = 0.01], and prolonged the interdosing intervals of ETN [+235% (38, 432); p = 0.02] and ADA [+28% (6, 51); p = 0.04]. Time to drug switch was accelerated (χ2 = 6.03, p = 0.01). No group differences in adverse events, disease activity, or self-reported outcomes were shown, indicating equally sustained remission. CONCLUSIONS: TDM reduced prescription of IFX, ETN, and ADA and identified patients benefiting from accelerated drug switch, thereby minimizing treatment failure, risk of toxicity, and unnecessary adverse events.

Wavelength optimization for the laser treatment of port wine stains.

Based on the well-known principle of selective photothermolysis, laser has been a promising way for the treatment of port wine stains (PWSs). The laser wavelengths used for PWS's clinical treatment include but are not limited to pulsed dye laser (PDL) in 585-600 nm, long-pulse 755-nm alexandrite, and 1064-nm Nd:YAG lasers. The objective of this study was to investigate the optimal wavelength for PWS's laser treatment. A two-scale mathematic model was constructed to simultaneously quantify macroscale laser energy attenuation in two-layered bulk skin and microscale local energy absorption on target blood vessels within Krogh unit. The effects of morphological parameters, including epidermal melanin content, epidermal thickness, dermal blood content, blood vessel depth, and diameter on laser energy deposition within target blood vessels, were investigated from the visible to near-infrared bands (500-1100 nm). The energy deposition ratio of target blood vessel to epidermal surface was proposed to determine the optimal laser wavelength for PWS with different skin morphological parameters. The bioheat transfer modeling and animal experiment are also conducted to prove our wavelength optimization. The optimal wavelengths for lightly pigmented skin with small and shallow target blood vessels are 580-610 nm in the visible band. This wavelength coincides with commercially used PDL. The optimal wavelength shifts to 940 nm as the epidermal pigmentation increases or the size and blood vessel depth increases. The optimal wavelength changes to 1005 nm as the epidermal pigmentation or the size and burying depth of target blood vessel further increases. Nine hundred forty nanometers can be selected as a general wavelength in PWS treatment to meet the need in most widely morphological structure. Lasers with wavelengths in the 580-610, 940, and 1005 nm regions are effective for treating PWS because of their high optical selectivity in blood over the epidermis.

[Application of indocyanine green fluorescence visualization in surgical resection of abdominal wall endometriosis].

Objective: To investigate the feasibility, effectiveness and safety of indocyanine green (ICG) navigation in the surgical resection of abdominal wall endometriosis (AWE). Methods: Seven women undergoing surgery for AWE in First Affiliated Hospital of Sun Yat-sen University (from July 1, 2021 to October 1, 2021) were collected. After exposure of the focus, ICG were used intravenously (0.25 mg/kg) as fluorescent dye for the intraoperative evaluation of AWE vascularization. Resection of the AWE was guided by direct visualization of the focus under standard laparoscopy with a near-infrared (NIR) camera head. Surgical margin around the AWE (3, 6, 9 and 12 point) and the margin under the focus were obtained for postoperative pathological examination of endometriosis. Time from injection to fluorescence visualization, the proportion of fluorescence visualization, time of fully resection of AWE, side effects related to the use of ICG, perioperative complications as well as the pathological result of the surgical margins were recorded. Results: ICG fluorescence of the AWE were seen in 5 patients (5/7). The mean time from injection to fluorescence visualization was (46.7±9.8) s. The mean time of fully resection of AWE was (16.4±7.0) minutes. There were no side effects related to the use of ICG. The rate of class-A wound healing was 7/7. All of the surgical margins were confirmed endometriosis-negative by postoperative pathological examination. Conclusion: ICG fluorescence visualization could conduct accurate resection of AWE, which is clinically safe and effective.

Maintenance treatment in advanced HER2-negative gastric cancer.

Survival for patients with advanced gastric cancer (GC) remains poor. Systemic chemotherapy which has reached a plateau stays the standard first-line (1L) treatment for advanced human epidermal growth-factor receptor 2 (HER2)-negative GC. To maximize the benefit of 1L treatment, the concept of maintenance treatment is constantly being explored. In advanced HER2-negative GC, current clinical guidelines do not recommend a standard maintenance therapy strategy. In addition to the monotherapy maintenance with fluorouracil after 4-6 cycles of 1L chemotherapy, some agents that are active against novel targets have been evaluated in clinical trials for maintenance treatment. Whereas most of these trials do not reach their primary endpoints, they open new horizons for the 1L treatment of advanced HER2-negative GC. Therefore, we reviewed the clinical trials in the field of maintenance treatment in advanced HER2-negative GC and discussed some of the problems in clinical trials.

Circular RNA circCNOT6L regulates cell development through modulating miR-384/FN1 axis in esophageal squamous cell carcinoma.

OBJECTIVE: In recent years, circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to be related to the development of esophageal squamous cell carcinoma (ESCC). However, their functional mechanisms remain to be investigated. Herein, we focus our research on the functions and mechanisms of circCNOT6L and miR-384 in ESCC. MATERIALS AND METHODS: The levels of circCNOT6L, miR-384, and fibronectin 1 (FN1) were determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RNase R was used to investigate circCNOT6L stabilization. Cell proliferation and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Western blot assay was employed to analyze the protein levels of FN1, proliferation-related genes, and iron metabolism-related genes. In addition, the interaction between miR-384 and circCNOT6L or FN1 was predicted by starBase3.0 and confirmed by the Dual-Luciferase reporter assay. Mouse xenograft was carried out to measure the effect of circCNOT6L on tumor growth in vivo. RESULTS: CircCNOT6L and FN1 levels were upregulated, and miR-384 level was downregulated in ESCC tissues/cells. CircCNOT6L knockdown attenuated ESCC cell proliferation and iron metabolism disorder, as well as accelerated apoptosis. Notably, circCNOT6L targeted miR-384, and miR-384 targeted FN1. MiR-384 depletion and FN1 upregulation weakened the effects of circCNOT6L knockdown and miR-384 overexpression on ESCC cell progression, respectively. Besides, circCNOT6L knockdown inhibited tumor growth in vivo. CONCLUSIONS: Our results demonstrated that circCNOT6L positively regulated the development of ESCC cells via modulating miR-384/FN1 axis. Our findings provided a theoretical basis for the therapy of ESCC patients.

Reduced c-Fos expression in orexin neurons of the lateral hypothalamic area and the locus coeruleus following injection of spinosin into mice.

BACKGROUND: Spinosin, a major component of Samen Ziziphi spinosae, has been shown to modulate sedation and hypnosis; however, the underlying neuronal mechanisms of its stimulatory effects remain unclear. MATERIALS AND METHODS: In the present study, we injected spinosin (15 mg/kg) or saline into mice, which were killed after 90 min. We isolated the brains, which were immunohistochemically stained for c-Fos as a biomarker for neuronal activation and assessed the expression profile of c-Fos in various sleep-arousal brain areas. RESULTS: Our findings revealed that there were no statistically significant differences in the expression of c-Fos in the nucleus accumbens and ventrolateral preoptic area, the vertical limb of the diagonal band nucleus, horizontal limb of the diagonal band nucleus, ventral tuberomammillary nucleus, ventral tegmental area, and dorsal raphe nucleus relative to saline between saline and spinosin-treated mice. Unlike saline, spinosin markedly decreased c-Fos expression in the lateral hypothalamic area (LHA) as well as the locus coeruleus (LC). Compared to the saline injection, the application of spinosin also resulted in a marked decrease in c-Fos expression in the LHA orexin neurons. CONCLUSIONS: These findings suggest that spinosin administration results in a restricted pattern of c-Fos expression within the LHA orexin neurons and the LC, suggesting that this particular neuronal inactivation contributes to sedation and hypnosis.

Shock-Induced Damage and Dynamic Fracture in Cylindrical Bodies Submerged in Liquid.

Understanding the response of solid materials to shock loading is important for mitigating shock-induced damages and failures, as well as advancing the beneficial use of shock waves for material modifications. In this paper, we consider a representative brittle material, BegoStone, in the form of cylindrical bodies and submerged in water. We present a computational study on the causal relationship between the prescribed shock load and the resulting elastic waves and damage in the solid material. A recently developed three-dimensional computational framework, FIVER, is employed, which couples a finite volume compressible fluid solver with a finite element structural dynamics solver through the construction and solution of local, one-dimensional fluid-solid Riemann problems. The material damage and fracture are modeled and simulated using a continuum damage mechanics model and an element erosion method. The computational model is validated in the context of shock wave lithotripsy and the results are compared with experimental data. We first show that after calibrating the growth rate of microscopic damage and the threshold for macroscopic fracture, the computational framework is capable of capturing the location and shape of the shock-induced fracture observed in a laboratory experiment. Next, we introduce a new phenomenological model of shock waveform, and present a numerical parametric study on the effects of a single shock load, in which the shock waveform, magnitude, and the size of the target material are varied. In particular, we vary the waveform gradually from one that features non-monotonic decay with a tensile phase to one that exhibits monotonic decay without a tensile phase. The result suggests that when the length of the shock pulse is comparable to that of the target material, the former waveform may induce much more significant damage than the latter one, even if the two share the same magnitude, duration, and acoustic energy.

Characterization of Novel Murine and Human PDAC Cell Models: Identifying the Role of Intestine Specific Homeobox Gene ISX in Hypoxia and Disease Progression.

Therapy failure and metastasis-associated mortality are stumbling blocks in the management of PDAC in patients. Failure of therapy is associated to intense hypoxic conditions of tumors. To develop effective therapies, a complete understanding of hypoxia-associated changes in genetic landscape of tumors during disease progression is needed. Because artificially immortalized cell lines do not rightly represent the disease progression, studying genetics of tumors in spontaneous models is warranted. In the current study, we generated a spectrum of spontaneous human (UM-PDC1; UM-PDC2) and murine (HI-PanL, HI-PancI, HI-PanM) models representing localized, invasive, and metastatic PDAC from a patient and transgenic mice (K-rasG12D/Pdxcre/Ink4a/p16-/). These spontaneous models grow vigorously under hypoxia and exhibit activated K-ras signaling, progressive loss of PTEN, and tumorigenicity in vivo. Whereas UM-PDC1 form localized tumors, the UM-PDC2 metastasize to lungs in mice. In an order of progression, these models exhibit genomic instability marked by gross chromosomal rearrangements, centrosome-number variations, Aurora-kinase/H2AX colocalization, loss of primary cilia, and α-tubulin acetylation. The RNA sequencing of hypoxic models followed by qRT-PCR validation and gene-set enrichment identified Intestine-Specific Homeobox factor (ISX)-driven molecular pathway as an indicator PDAC aggressivness. TCGA-PAAD clinical data analysis showed high ISX expression correlation to poor survival of PDAC patients, particularly women. The functional studies showed ISX as a regulator of i) invasiveness and migratory potential and ii) VEGF, MMP2, and NFκB activation in PDAC cells. We suggest that ISX is a potential druggable target and newly developed spontaneous cell models are valuable tools for studying mechanism and testing therapies for PDAC.

Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device.

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.

Predictors of Early and Late Mortality in Older Kidney Transplant Recipients.

BACKGROUND: Older kidney patients with chronic kidney disease benefit significantly from kidney transplantation. However, these older transplant recipients have greater mortality after transplantation than younger transplant recipients. Understanding the impact of comorbidities on post-transplant mortality can improve risk stratification and patient selection. METHODS: A single-center analysis of 3105 kidney transplant recipients was performed over a 12-year period. Comorbidities associated with death were evaluated in older and younger transplant recipients. RESULTS: The 2 most important factors associated with increased mortality in the first 100 days after transplant were recipient age ≥60 and receipt of deceased donor organs (adjusted odds ratios, 3.29 and 5.80, respectively), with no statistically significant impact of recipient comorbidities. In the later post-transplant period (after the first 100 days), recipient age ≥60 and receipt of deceased donor organs (adjusted hazard ratios [HR] of 2.14 and 2.29, respectively) remained predictors of mortality. We also found that donor age ≥60 and the recipient having cardiovascular disease and diabetes were independent predictors of increased mortality. There was a statistically significant interaction between diabetes and heart disease and recipient age ≥60, with a lesser impact on late mortality in older patients compared to younger patients. CONCLUSIONS: This analysis suggests that comorbidities have a larger impact later after transplantation, with less effect on older recipients. These observations suggest that certain comorbid conditions should be evaluated differently in older patients compared to younger ones.

[Impact of cessation of antiviral therapy at delivery on postpartum liver function in mothers with chronic hepatitis B virus infection].

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ(2) = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion: Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.

The biomechanical properties of the urethra in boys with hypospadias: a preliminary study.

PURPOSE: The ventral aspect of the penis in boys with hypospadias is composed of dysplastic tissue of the skin and the urethra. The aim of this study was to assess the pre-operative size and biomechanical properties of urethrae in boys with and without hypospadias using a more objective catheter-based system. MATERIALS & METHODS: In this non-blinded clinical observation study, the study population consisted of 19 boys with hypospadias-the case group (median age 13.9 months [range: 12.2-21.3])-and seven boys without hypospadias-the control group (median age 8.5 months [range: 3.8-18.1]). Modified measurements of impedance were used to assess the size, compliance and viscoelasticity of the urethrae under stepwise increased pressures (between 0, 40 and 60 cmH2O) using a customised Endolumenal Functional Lumen Imaging probe (EndoFLIP®). RESULTS: The sizes of the urethrae in boys with hypospadias are variable but tend towards being narrower and less compliant than those of the control subjects i.e. median diameter for meatus urethra was 3.2 mm (range: 2.98-3.92) in the hypospadias group compared with 3.64 (range: 3.22-4.44) in the control group at 40 cmH2O, and the median change in diameter at meatus urethra was 0.08 mm (range: -0.02 to 0.52) in the hypospadias group compared with 0.23 mm (range: -0.02 to 0.34) when the pressure was increased from 40 to 60 cmH2O. This biomechanical analysis found that there was no significant viscoelasticity of the urethral meatus in both the groups, whereas the remainder of the urethral structure generally had viscoelastic properties in the control group, seen as a creep on the time/diameter curves (Figure). In the group of boys with hypospadias, evaluations of the urethrae revealed varying viscoelastic abilities, ranging from abilities that were comparable with those of the control subjects to no sign of viscoelasticity at all. CONCLUSIONS: This study is the first to measure the biomechanical properties of the urethra in children, which might help to provide an understanding as to the structural and functional changes associated with hypospadias. The urethrae in the subjects with hypospadias were variable in diameter but tended to be narrower overall, especially in the distal portion of the urethra. Furthermore, the urethrae in boys with hypospadias were frequently less viscoelastic than those of controls. CLINICAL RELEVANCE: The EndoFLIP® system may be a future way of objectively estimating the severity of a urethral obstruction and could potentially be included in the postoperative assessment of patients with signs of hampered voiding.

Childhood obesity, weight loss and developmental trajectories predict the persistence and remission of childhood sleep-disordered breathing.

BACKGROUND: Obesity has been recognized as a risk factor for childhood sleep-disordered breathing (SDB), yet it remains unclear how obesity and weight change predict the course of childhood SDB. OBJECTIVE: The objective of the study is to investigate the role of body weight, upper airway abnormalities and developmental trajectories on the persistence and remission of childhood SDB in the transition to adolescence. METHODS: The Penn State Child Cohort is a representative population sample of 700 children (5-12 years), of whom 421 were followed up as adolescents (12-23 years). Participants underwent a clinical history, physical examination and polysomnography at both time points. RESULTS: Obesity and enlarged tonsils were cross-sectionally associated with childhood SDB. Longitudinally, baseline obesity predicted the persistence of childhood SDB (OR = 3.75, 95% CI = 2.00-7.05), while weight loss predicted its remission (OR = 1.67, 95% CI = 1.11-2.50). Children with enlarged tonsils who remitted from SDB had not experienced significant weight loss and only 4.4% had undergone adeno/tonsillectomy. Body fat distribution/composition at follow-up was similar in those who had remitted from childhood SDB as compared with those who had never experienced SDB, while those who persisted with childhood SDB showed significant android distribution and visceral adiposity at follow-up. CONCLUSIONS: Our data support a causal role for obesity and weight loss in the chronicity and remission, respectively, of childhood SDB in the transition to adolescence and suggest that remission of SDB is related to developmental trajectories of the upper airway in a significant proportion of children. Thus, targeting childhood obesity and weight gain should be a priority in the prevention and treatment of SDB during this critical developmental period.

iTRAQ and PRM-based quantitative proteomics in T2DM-susceptible and -tolerant models of Bama mini-pig.

Type 2 diabetes mellitus (T2DM) is a complex, multifactorial metabolic disease, and the number of patients with T2DM has continued to increase in recent years. Large-scale proteomic studies on animal models of T2DM are of great importance to understand the pathophysiology of T2DM. Therefore, in our study, Isobaric tags for relative and absolute quantification (iTRAQ) and Parallel reaction monitoring (PRM) were used for proteomic analysis of skeletal muscles from T2DM-susceptible and -tolerant Bama mini-pig models induced by a high-fat, high-sugar diet. In our proteomic analysis, a total of 1646 proteins and 13 differentially expressed proteins (DEPs) were identified by iTRAQ-mass spectrometry, and 6 differentially expressed proteins were validated by PRM. Gene Ontology (GO) analysis revealed that most DEPs were extracellular matrix (ECM) proteins and participated in several biological processes, such as negative regulation of JAK-STAT cascade, negative regulation of STAT cascade, roundabout signaling pathway and peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan, and the molecular functions of roundabout binding, glycosaminoglycan binding, heparin binding, sulfur compound binding, collagen binding, and kinase inhibitor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that the differentially expressed proteins were involved in 14 pathways, including human disease pathways, metabolic pathways, signal transduction pathways, signaling molecules and interaction pathways, and the cellular process pathways associated with phagosomes and focal adhesion. In conclusion, the proteomics based on iTRAQ and PRM in T2DM-susceptible and -tolerant Bama mini-pig models showed that changes in amino acid metabolism, inflammation-associated pathways and the impaired function and environment of extracellular matrix are risk factors associated with increased pathogenesis of T2DM in Bama mini-pig.

Regional Cerebral Blood Flow in Mania: Assessment Using 320-Slice Computed Tomography.

Objectives: While evidence that episodes of mania in bipolar I are associated with changes in bioenergetic and regional cerebral blood flow (rCBF) and cerebral blood flow velocity (rCBFV), both the regions and the extent of these changes have not yet been defined. Therefore, we determined the pattern of regional cerebral perfusion mania patients and using patients with major depressive disorder (MDD) as positive controls and healthy participants as negative controls. Methods: Twenty participants with mania, together with 22 MDD patients and 24 healthy volunteers, were recruited for this study. On all participants, Transcranial Doppler (TCD) was conducted to measure rCBFV parameters, 320-slice CT was conducted to measure rCBF in the different cerebral artery regions, and hematological parameters were assessed. ANOVA and Pearson's tests were used for the statistical analysis. Results: Our data indicated that rCBF in the medial temporal lobe and hippocampus, especially in the left medial temporal lobe and the right hippocampus, was increased in the mania group compared with the control and MDD groups (p < 0.01). In contrast, rCBF in the medial temporal lobe and hippocampus was decreased in the depression group (p < 0.01) compared with healthy controls. In addition, values of rCBFV in the bilateral internal carotid arteries (ICAs) and middle cerebral arteries (MCA) were increased in mania (p < 0.01) in comparison to the MDD group. Whole blood viscosity and hematocrit as well as red blood cell sedimentation rate remained unchanged in all group (p > 0.05). Conclusions: In mania, rCBF is increased in the medial temporal lobe and hippocampus, with a corresponding increase in rCBFV in the same regions.

[Staged transcranial and transsphenoidal surgery for giant pituitary adenomas: a retrospective study of 21 cases].

Objective: To investigate the effect of the second-stage transcranial and transsphenoidal approach for giant pituitary tumors. Methods: A retrospective review of 21 patients, who had undergone the transcranial surgery and then transsphenoidal surgery for giant pituitary adenomas from 2012 to 2015 in the neurosurgery department of West China Hospital, was performed. Visual findings, endocrine presentation, complications, and tumor types were collected. All data were based on clinical feature, MRI, and follow-up. Results: Among the 21 cases, gross total resection of tumor was achieved in 7 of all patients, subtotal in 11, and partial in 3. No intracranial hemorrhage or death occurred postoperatively. Postoperative infectionoccurred in one patient and cerebrospinal fluid leakage occurred in 3 patients. Four patients recovered after treatment. Conclusion: According to the clinical feature and MRI, it is safe and effective to choose the transcranial surgery and then transsphenoidal surgery for specific giant pituitary adenomas, which can improve treatment effects and reduce postoperative complications.

Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case-control studies.

PURPOSE: Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women's susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (- 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk. METHODS: All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. RESULTS: A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 - 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56-0.92); homozygote, 0.51 (0.32-0.82); heterozygote, 0.44 (0.25-0.78); and dominant 0.47 (0.29-0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41-0.93)] and recessive model [0.61 (0.37-0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39-0.98)] and dominant model [0.63 (0.41-0.96)]. CONCLUSIONS: Our study has shown that PON1 - 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.