[The relationship between differentially expressed thyroid cancer genes and clinical characteristics in metastatic children and adolescents].

Objective: To investigate the relationship between genes and clinical characteristics in children and adolescents with metastatic differentiated thyroid cancer (caDTC). Methods: A cross sectional study. A total of 67 caDTC patients with lymph node metastasis or distant metastasis in Peking Union Medical College Hospital from December 2020 to December 2022 were included, according to the inclusion and exclusion criteria. Then the differences in clinicopathologic features and iodine intake were compared among different genomes, and the age subgroups divided by the age of 12 were further analyzed. Results: Among the 67 cases of caDTC, the diagnosed age [M(Q1, Q3)]was 13.2 (9.7, 16.9) years old, with 23 males and 44 females. There were 68.7% (46/67) of patients have distant metastasis (M1 stage). Pathogenic or potentially pathogenic gene variants were detected in 68.7% (46/67) of the patients, with RET or NTRK fusion (RET/NTRK) being the most common [43.3%(29/67)], BRAF V600E mutation followed [19.4%(13/67)].There was only 1 caDTC with NRAS Q61R mutation. The patients were divided into RET/NTRK fusion group (n=29), BRAF mutation group (n=12), other mutation group (n=4), and non-mutation group (n=21) (1 patient was not included in the gene mutation subgroup comparison due to the presence of NRAS Q61R mutation and BRAF V600E mutation). The comparison of gene feature groups showed that compared to the BRAF mutation group, caDTC with RET/NTRK fusion tended to have a lower age at diagnosis [12.6(9.3, 15.9) vs 17.2(15.5, 18.1) years old, P<0.001], the proportion of mutation load≥2 was higher (10.4% vs 8.3%, P=0.027), with statistically significant difference. Among 46 M1 stage patients, 71.7% (33/46) had initial iodine intake, and 30.4% (14/46) developed radioiodine-refractory (RAIR). In age group comparison, the<12 year old group had a higher proportion of male patients (51.9% vs 22.5%, P=0.013) and a lower incidence of BRAF V600E mutations (0 vs 32.5%, P<0.001) compared to the≥12 year old group, and the differences were statistically significant. Conclusions: The incidence of RET/NTRK fusion ranks first in metastatic caDTC, featured with younger age at diagnosis and higher rate of distant metastasis. Although most metastatic lesions initially consume iodine, they are prone to RAIR. Attention should be paid to the potential role of RET/NTRK fusion in the invasion and iodine resistance of young caDTC patients.

Evaluation and Management of Indeterminate Pulmonary Nodules on Chest Computed Tomography in Asymptomatic Subjects: The Principles of Nodule Guidelines.

With the rapidly increasing number of chest computed tomography (CT) examinations, the question of how to manage lung nodules found in asymptomatic patients has become increasingly important. Several nodule management guidelines have been developed that can be applied to incidentally found lung nodules (the Fleischner Society guideline), nodules found during lung cancer screening (International Early Lung Cancer Action Program protocol [I-ELCAP] and Lung CT Screening Reporting and Data System [Lung-RADS]), or both (American College of Chest Physicians guideline [ACCP], British Thoracic Society guideline [BTS], and National Comprehensive Cancer Network guideline [NCCN]). As the radiologic nodule type (solid, part-solid, and pure ground glass) and size are significant predictors of a nodule's nature, most guidelines categorize nodules in terms of these characteristics. Various methods exist for measuring the size of nodules, and the method recommended in each guideline should be followed. The diameter can be manually measured as a single maximal diameter or as an average of two-dimensional diameters, and software can be used to obtain volumetric measurements. It is important to properly evaluate and measure nodules and familiarize ourselves with the relevant guidelines to appropriately utilize medical resources and minimize unnecessary radiation exposure to patients.

Isolating Anthropogenic Wetland Loss by Concurrently Tracking Inundation and Land Cover Disturbance across the Mid-Atlantic Region, U.S.

Global trends in wetland degradation and loss have created an urgency to monitor wetland extent, as well as track the distribution and causes of wetland loss. Satellite imagery can be used to monitor wetlands over time, but few efforts have attempted to distinguish anthropogenic wetland loss from climate-driven variability in wetland extent. We present an approach to concurrently track land cover disturbance and inundation extent across the Mid-Atlantic region, United States, using the Landsat archive in Google Earth Engine. Disturbance was identified as a change in greenness, using a harmonic linear regression approach, or as a change in growing season brightness. Inundation extent was mapped using a modified version of the U.S. Geological Survey's Dynamic Surface Water Extent (DSWE) algorithm. Annual (2015-2018) disturbance averaged 0.32% (1095 km2 year-1) of the study area per year and was most common in forested areas. While inundation extent showed substantial interannual variability, the co-occurrence of disturbance and declines in inundation extent represented a minority of both change types, totaling 109 km2 over the four-year period, and 186 km2, using the National Wetland Inventory dataset in place of the Landsat-derived inundation extent. When the annual products were evaluated with permitted wetland and stream fill points, 95% of the fill points were detected, with most found by the disturbance product (89%) and fewer found by the inundation decline product (25%). The results suggest that mapping inundation alone is unlikely to be adequate to find and track anthropogenic wetland loss. Alternatively, remotely tracking both disturbance and inundation can potentially focus efforts to protect, manage, and restore wetlands.

Dietary selenomethionine increases antioxidant capacity of geese by improving glutathione and thioredoxin systems.

A total of 200 healthy 28-day-old male Jiangnan White geese were used to investigate the free radical scavenging ability, reduced glutathione (GSH) and thioredoxin systems, and the concentrations of reactive oxygen metabolites (ROM), malondialdehyde (MDA), and protein carbonyl (PC) in geese fed diets with organic selenium (Se) (Selenomethionine, SeMet) and inorganic Se (sodium selenite, SS). All geese were randomly allotted into 4 groups with 5 replicates of 10 geese each, and received basal diet supplemented with 0.3 mg Se/kg SS, 0.2, 0.3 and 0.4 mg Se/kg SeMet until 70 D of age, respectively. Geese in the SS and SeMet groups exhibited similar growth performance. Diet with SeMet increased the scavenging abilities of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt free radical (ABTS•+, P < 0.001) and superoxide radical (O2-•, P = 0.002) in the serum of geese, as well as the scavenging abilities of ABTS•+ (P = 0.023), hydroxyl radical (P = 0.009) and O2-• (P = 0.019) in the liver of geese. Compared to the SS group, SeMet increased hepatic GSH concentration (P = 0.002), the activities of glutathione peroxidase (P = 0.031), γ-glutamate cysteine ligase (P < 0.001), and thioredoxin reductase (P < 0.001), and decreased the concentrations of ROM, MDA, and PC in the serum and liver of geese (P < 0.05). In conclusion, dietary SeMet inclusion would be more effective than SS in increasing the antioxidant capacity of geese, possibly by improving GSH and thioredoxin systems, and 0.2 mg Se/kg SeMet in goose diet is recommended.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease]. / Osobennosti tserebral'nogo metabolizma gliukozy u bol'nykh s kognitivnymi narusheniiami pri bolezni Parkinsona.

AIM: To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. MATERIAL AND METHODS: Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). RESULTS AND CONCLUSION: In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Genome-wide association study of loss of heterozygosity and metastasis-free survival in breast cancer patients.

One of the factors providing the diversity and heterogeneity of malignant tumors, particularly breast cancer, are genetic variations, due to gene polymorphism, and, especially, the phenomenon of loss of heterozygosity (LOH). It has been shown that LOH in some genes could be a good prognostic marker. AIM: To perform genome-wide study on LOH in association with metastasis-free survival in breast cancer. MATERIALS AND METHODS: The study involved 68 patients with breast cancer. LOH status was detected by microarray analysis, using a high density DNA-chip CytoScanTM HD Array (Affymetrix, USA). The Chromosome Analysis Suite 3.1 (Affymetrix, USA) software was used for result processing. RESULTS: 13,815 genes were examined, in order to detect LOH. The frequency of LOH varied from 0% to 63%. The association analysis identified four genes: EDA2R, PGK1, TAF9B and CYSLTR1 that demonstrated the presence of LOH associated with metastasis-free survival (log-rank test, p < 0.03). CONCLUSIONS: The presence of LOH in EDA2R, TAF9B, and CYSLTR1 genes is associated with metastasis-free survival in breast cancer patients, indicating their potential value as prognostic markers.

Columnar structured FePt films epitaxially grown on large lattice mismatched intermediate layer.

The microstructure and magnetic properties of the FePt films grown on large mismatched ZrN (15.7%) intermediate layer were investigated. With using ZrN intermediate layer, FePt 10 nm films exhibited (001) texture except for some weaker FePt (110) texture. Good epitaxial relationships of FePt (001) <100>//ZrN (001) <100>//TiN (001) <100> among FePt and ZrN/TiN were revealed from the transmission electron microscopy (TEM) results. As compared with TiN intermediate layer, although FePt-SiO2-C films grown on ZrN/TiN intermediate layer showed isotropic magnetic properties, the large interfacial energy and lattice mismatch between FePt and ZrN would lead to form columnar structural FePt films with smaller grain size and improved isolation. By doping ZrN into the TiN layer, solid solution of ZrTiN was formed and the lattice constant is increased comparing with TiN and decreased comparing with ZrN. Moreover, FePt-SiO2-C films grown on TiN 2 nm-20 vol.% ZrN/TiN 3 nm intermediate layer showed an improved perpendicular magnetic anisotropy. Simultaneously, columnar structure with smaller grain size retained.

Beneficial effects of early hemostasis on spinal cord injury in the rat.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the effect of early hemostasis on spinal cord injury (SCI). SETTING: Fourth Military Medical University, Xi'an, China. METHODS: Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg-1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg-1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso-Beattie-Bresnahan scoring and rump height index assay were used to examine locomotion recovery. RESULTS: Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats. CONCLUSION: The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice.

[PNEUMOCOCCAL VACCINE IN ADULTS REDUCES THE RISK OF INFECTIONS CAUSED BY STREPTOCOCCUS PNEUMONIAE].

Streptococcus pneumoniae is a major cause of severe disease worldwide, particularly in the risk population. Two pneumococcal vaccines are currently available for specific prevention of pneumococcal infections among adults in Russia: a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). The article describes modern views on the effectiveness and safety of two pneumococcal vaccines in adults with underlying medical conditions and adults aged ≥ 65 years and provides current recommendations for routine use of PPSV23 and PCV13 among persons included in the risk group.

[Choosing a method of draining the upper urinary tract following percutaneous nephrolithotripsy].

PURPOSE: to compare various methods of upper urinary tract drainage in patients with urolithiasis. PATIENTS AND METHODS: 60 patients were included into a prospective study which ran from March 2013 through December 2014. All patients underwent PCNL with a nephrostomy tract diameter of (28-30 Ch.) at the I.M. Sechenov First Moscow State Medical University urology clinic. Patients were divided into 2 groups. Group 1 30 (patients) underwent nephrostomy after PCNL with nephrostomy tract placement, in group 2 (29 patients) internal drainage was performed. One patient withdrew from the study due to residual stone. Adequacy of urinary tract draining was assessed by operative time and blood loss. A comparative analysis was performed to outline difference in both groups by length of hospital stay, severity of flank pain in early postoperative period and 5 days after the procedure, day of drain removal. RESULTS: the average operative time in group No1 was 104 minutes (+/-17 min.), and 71 minutes (+/- 19 minutes) in group No2 . The average hemoglobin level before surgery in both groups was roughly comparable and amounted to: 141.5g / l (+/-13) in group No1, in group No 2 143.6 g / l (+/-18). At the same time, hemoglobin level in the early postoperative period varied in both groups and was as follows: 121g / l (+/-13) in group No1, and 128g / l (+/-14) in group 2. Evaluation of pain severity by VAS score showed that severity of pain in an early postoperative period was roughly comparable in both groups and amounted to 6.29 and 6.05 points, respectively, but from the second day, and since the activation of the patients, the values of the intensity of pain in both groups became differ. Group No1: - 5.33 (+/-1.5) on day 2, 3.25 (+/-1.8) on day 3, - 2.5 (+/-1.6) on day 5. A more thorough elucidation of the cause of pain showed that in 56 (88%) patients the pain was due to the nephrostomy and pain in the nephrostomy stroke while driving and only 7 (11%) patients complained of a pain in the operated kidney. Group No2: - 3.5 (+/-1.2) on day 2, - 2.9 (+/-1.4) on day 3, 1.22 (+/-0.8) on day 5. CONCLUSION: A detailed and thorough history, taking together with multislice computed tomography and multiplanar 3D modeling allows for better preoperative assessment regarding a size, a number and location of stones, vascular architecture of the kidney. This enebles an experienced endoscopic surgeon to plan an operation, and avoid the possible difficulties associated with lithotripsy and choose a more suitable method of pyelocaliceal system draining after the operation. In turn, tubeless PCNL, with proper intraoperative managamant and careful selection of patients appears to be safe and effective. Drainage of the upper urinary tract with internal drainage reduces intensity of postoperative pain, which improves the quality of life of patients in the postoperative period, and reduces the length of postoperative stay.

[THE ROLE OF 3D-COMPUTER SIMULATION IN IMPROVING THE STAGHORN NEPHROLITHIASIS TREATMENT RESULTS].

This article presents the experience of applying 3D-computer simulation for treatment planning in patients with coral kidney stones. The impact of the kidney internal structure and the nephrolithiasis stage on the treatment results of the patients with staghorn stones are analyzed on the basis of authors' own experience. They note the usefulness of computer modeling in preoperative planning for improving the treatment results and preventing intraoperative complications.

[3D-TECHNOLOGIES AS A CORE ELEMENT OF PLANNING AND IMPLEMENTATION OF VIRTUAL AND ACTUAL RENAL SURGERY].

The purpose of this article is to demonstrate the role of modern computer technologies in performing virtual and actual renal tumor surgery. Currently 3D modeling makes it possible to clearly define strategy and tactics of an individual patient treatment.

[UROLOGY LESSONS FOR COLORECTAL SURGEONS].

The anatomical and functional relationship of the pelvic organs is a prerequisite to the development of complications when performing surgical procedures in this anatomical region. Prevention and timely diagnosis of intraoperative injuries of both the urinary system organs and intestine, as well as well-coordinated work of urologist and colorectal surgeon team offer the opportunity to employ optimal tactics for the patient management.

Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury.

Microglia/macrophages play a crucial role in inflammation after spinal cord injury (SCI). Although extensive studies have been performed on the mechanisms of microglia/macrophage activation and recruitment, how microglia/macrophages are eliminated remains unclear. In the present study, we observed a high-level expression of mixed lineage kinase domain-like protein (MLKL), a key molecule in the execution of necroptosis, in microglia/macrophages after SCI in mice. In vivo PI-labeling and Necrostatin-1 treatment confirmed the necroptosis of microglia/macrophages. Interestingly, our electronic microscopic (EM) study revealed that MLKL localized not only at the membrane but also on the endoplasmic reticulum (ER) of necroptotic microglia/macrophages. Furthermore, receptor-interacting protein 3 (RIP3), another necrosome component, was also found on the ER of necroptotic microglia/macrophages. And Glucose-regulated protein 78 (GRP78), an ER stress sensor, was up-regulated in MLKL-positive microglia/macrophages after SCI, suggesting a possible link between necroptosis and ER stress. In vitro, oxygen-glucose deprivation (OGD) stress induced ER stress and necroptosis in microglia. Inhibiting ER stress by 4-phenylbutyrate (4-PBA) significantly blocked the OGD-induced necroptosis of microglia. In the end, our data showed that, GRP78 and phosphorylated MLKL were co-expressed by the microglia/macrophages in the injured human spinal cord. Taken together, these results suggested that microglia/macrophages undergo an ER-stress involved necroptosis after SCI, implying that ER stress and necroptosis could be manipulated for modulating inflammation post-SCI.

[TISSUE-ENGINEERED SUBSTITUTION URETHROPLASTY BASED ON DECELLULARIZED VASCULAR MATRIX AND AUTOLOGOUS CELLS OF THE BUCCAL MUCOSA: THE FIRST EXPERIENCE].

Urethral strictures and anomalies remain a challenging urological problem. Reconstructive plastic surgery has been shown to be the most effective way to treat them. There are two main types of urethroplasty: anastomosis (anastomotic urethroplasty) and expansion of the urethral lumen using of flaps and grafts (substitution urethroplasty). Currently the ideal material for substitution urethroplasty does not exist. Tissue engineering of the urethra seems to be one of the most promising approaches to address this problem. Various tissues-engineering techniques were proposed for substitution urethroplasty. In this study, tissue-engineering design was based on the decellularized cadaveric arterial wall. The study results demonstrated the feasibility of creating stable tissue-engineered structures with autologous cultured epithelial cells of the buccal mucosa and decellularized matrix from human cadaveric arterial wall (DMCAW). There was a complete engraftment of tissue-engineering design based on DMCAW and buccal mucosa cells, used for substitution urethroplasty in a patient with the bulbar urethral stricture. Postoperatively (within 4 months after surgery) no complications and/or adverse events were observed. However, in the late postoperative period (12 months) there was recurrence of urethral stricture in the middle of the tissue-engineering design and the native urethra that warranted another surgery. Tissue-engineering design based on DMCAW and autologous buccal mucosa is safe as a material for substitution urethroplasty. Further research is required to ascertain the effectiveness of the method.

[URETERAL TISSUE ENGINEERING: CHALLENGES AND PROSPECTS].

A broad range of pathologic conditions of the ureter (strictures, obliterations, fistulas, and so on) requiring reconstructive plastic surgery is a challenging urological problem. A variety of approaches to solve the problem indicates the need of searching for new opportunities. A new direction in reconstructive surgery of the ureter is the tissue engineering. Tissue engineering involves the usage of matrices and cells. The matrices can be used both with cultured cells, and without them. This review represents the results of preclinical studies on feasibility of tissue engineering using as a matrix both natural and synthetic materials for different ureter impairments. Presently, there are no data on the use of tissue-engineering for the ureter reconstruction in clinical trials (i.e. involving human subjects). The results of studies presented in the review inspire certain optimism, but ureteral tissue-engineering is a difficult task requiring a balanced approach and well-thought-out design of preclinical studies.

[3D-TECHNOLOGY AS AN ELEMENT OF PLANNING, EFFECTIVE IMPLEMENTATION AND SURGICAL SIMULATION TRAINING IN STAGHORN NEPHROLITHIASIS MANAGEMENT].

Daily practice of a physician of any specialty is incomplete without an analysis of the data derived from the use of various imaging techniques. Over the past decade, there have been significant changes in the understanding of the clinical anatomy of the patient, which is largely the result of the introduction of modern computer technology in medicine.

[COMPUTER-ASSISTED SURGERY FOR RENAL TUMORS].

The main objective of this article is to show the role of modern computer technology in performing virtual and real surgical procedures for renal tumors. At the present time, 3D based modeling makes it possible to preoperatively identify individual strategy and tactics of treatment of a patient.

[TRANSURETHRAL CONTACT URETERAL LITHOTRIPSY IN A GASEOUS (CO2) MEDIUM].

The paper describes for the first time the method of contact ureteral lithotripsy in gaseous (CO2) medium. It presents the results of a comparative study of urolithiasis patients treated with this treatment modality (study group, n=30) and with traditional contact ureteral lithotripsy in liquid medium (control group, n=30). The incidence of retrograde migration of calculus in the kidney in the study group was 0%, while it was 16.6% in the control group. Acute or exacerbation of chronic pyelonephritis was diagnosed in only 3 (10%) patients in the control group. The suggested method of contact ureteral lithotripsy is safe and provides several advantages over traditional contact ureteral lithotripsy in a fluid medium, such as: physiologic validity, absence of calculus hypermobility (increased mobility), improved visualization during surgery and high cost effectiveness.