Plasma exosomes proteome profiling discovers protein markers associated with the therapeutic effect of Chaihu-Longgu-Muli decoction on temporal lobe epilepsy.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) uses Chaihu-Longgu-Muli decoction (CLMD) to alleviate disease, clear away heat, calm the mind, and temper excitation. It has been widely used for the therapy of neuropsychiatric disorders including epilepsy, dementia, anxiety, insomnia, and depression for several centuries in China. AIM OF THE STUDY: This study aims to analyze differentially expressed proteins (DEPs) in the plasma exosomes of patients with temporal lobe epilepsy (TLE) and after the Chaihu-Longgu-Muli Decoction (CLMD) therapy and to explore the biomarkers of TLE and the potential targets of CLMD in treating TLE. MATERIALS AND METHODS: The plasma exosomes of normal people and patients with TLE before the treatment of oxcarbazepine (OXC) and combined treatment of OXC and CLMD (OXC.CLMD) were harvested. The exosomes were separated from plasma through ultracentrifugation and then identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. The DEPs were analyzed by proteomics and then subjected to gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein level of key genes was detected using Western blot. A lithium chloride-pilocarpine-induced epilepsy rat model was established and treated with OXC alone, OXC. CLMD, and CLMD alone (low dose and high dose). Neuronal injury in the hippocampal dentate gyrus and ribosomal protein L6 (RPL6) expression in the brain tissues were detected using H&E staining, Nissl staining, and Western blot. RESULTS: The proteomic analysis showed several DEPs were present among plasma exosomes in the four groups; DEPs were enriched in epilepsy-related function and pathway. Four key proteins were screened, including RPL6, Nucleolin (NCL), Apolipoprotein A1 (APOA1), and Lactate Dehydrogenase A (LDHA). Among them, RPL6, NCL, and LDHA protein levels were downregulated and APOA1 protein level was upregulated in the plasma exosomes of TLE patients. After OXC and OXC. CLMD treatment, the protein level of RPL6, NCL, and LDHA was increased, and the APOA1 protein level was decreased. Moreover, the RPL6 protein level was further elevated after OXC. CLMD treatment than that after OXC treatment. In the TLE rat model, neuronal degeneration and necrosis in the hippocampal dentate gyrus increased and RPL6 expression level decreased. After the treatment with OXC, OXC. CLMD, and CLMD alone, the degeneration and necrosis of neurons decreased, and the RPL6 expression level was increased; RPL6 upregulation was remarkably obvious after CLMD treatment. CONCLUSIONS: RPL6, NCL, LDHA and APOA1 are the DEPs in the plasma exosomes of patients with TLE before and after therapy. RPL6 might be a potential biomarker of CLMD in treating TLE.

Sodium p-perfluorous nonenoxybenzene sulfonate induces ROS-mediated necroptosis by directly targeting catalase in HepG2 cells.

Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been widely used as a substitute for perfluorooctane sulfonic acid (PFOS) because of its high surface activity and low cost, but the knowledge of its biological effects is still limited. In this study, we compared the toxic effects of OBS and PFOS on human hepatoma cells (HepG2). OBS resulted in lower cell viability, higher ROS levels, and more severe necrosis than PFOS, indicating that OBS caused higher cytotoxicity than PFOS. In this process, OBS induced a burst of ROS and downregulation of catalase (CAT). OBS-induced oxidative stress was recovered after the CAT overexpression, but the CAT levels were not reversed after N-acetylcysteine (NAC) pretreatment. This indicates that the downregulated CAT is an upstream signal of the ROS burst. Moreover, drug affinity targeting assay, spectroscopic analysis and molecular docking were conducted, showing that OBS directly targeted CAT and therefore downregulated CAT. In addition, we found that OBS-induced necrosis is RIP1/RIP3-dependent programmed necroptosis. In summary, OBS directly targets CAT to reduce CAT levels and induces oxidative stress and necroptosis. Our findings are helpful to understand the toxicity of OBS and to evaluate the safety of OBS as a substitute for PFOS.

Fatal brainstem injury following proton radiation in a patient with medulloblastoma and a germline variant in RNF213.

Brainstem injury occurs secondary to radiation to the posterior fossa in up to 2% of pediatric patients. It may occur after months to years after treatment. It has been associated with age less than 5 years and with comorbid conditions such as cerebrovascular disease, diabetes mellitus, and hypertension. Radiation necrosis is often symptomatic and can be fatal. A pathogenic variant in RNF213 was found in a patient who suffered fatal radiation necrosis. This mutation has been associated with moyamoya disease and may predispose to radiation necrosis.

Granulomatous mastitis: A diagnostic challenge-3 year single institutional experience.

BACKGROUND: Granulomatous mastitis (GM) is often clinico-radiologically misdiagnosed as breast malignancy. Tuberculosis, foreign body reactions, fungal and parastic infections, and autoimmune diseases can cause GM. The present study aimed to assess the spectrum of GM on fine-needle aspiration biopsy (FNAB) smears along with its histopathological and clinico-radiological findings. MATERIALS AND METHODS: It was a retrospective study which included all cases of GM diagnosed on FNAB over a period of 3 years. The histopathological diagnosis was retrieved, wherever possible. All the FNA smears and histopathological sections were reviewed for the presence of epithelioid granulomas, necrosis, epithelioid histiocytes, inflammatory cells including plasma cells, neutrophils, eosinophils, multinucleated giant cells, and epithelial component and associated atypia, if any. The inflammatory cells and multinucleated giant cells were graded on a scale of 0 to 3+ in every case. RESULTS: Among the 22 cases evaluated, the most common inflammatory infiltrate was lymphocyte followed by neutrophils and eosinophils. Caseous necrosis was appreciated in 7 (31.8%) cases, out of which 5 (22.7%) were diagnosed as tubercular mastitis on FNA smears. Ziehl Neelson stain was done in all FNAB smears and AFB was positive in 7 (31.8%) cases. Histopathological correlation was available for 14 cases (63.6%). The most common diagnosis on histopathology was idiopathic GM having lobulo-centric granulomatous inflammation, epithelioid histiocytes, neutrophils, and lymphocytes. CONCLUSION: FNAB is a reliable and minimally invasive tool to diagnose tubercular mastitis, idiopathic GM and also ruling out clinicoradiological suspicion of malignancy. Careful examination of cytological smears can prevent an unnecessary biopsy in granulomatous lesions of breast.

Association between bacterial pathogenicity, endometrial histological changes and clinical prognosis in canine pyometra.

Despite the high frequency and clinical relevance of canine pyometra, its pathogenesis remains poorly understood. In this study, the clinical data, histopathological alterations, and microbiological findings of 39 dogs with pyometra were analyzed to assess possible associations. The mean age of the affected animals was 9.6 ± 3.8 years; 76.3 % (29/38) had open cervix pyometra, 88 % (22/25) had tachypnea, 71 % (27/38) had anorexia, and 60.5 % (23/38) had leukocytosis. Histopathological analysis revealed that 66.5 % (26/39) of the uteri had a high degree of inflammation (score 4). Third-degree hyperplasia of the endometrial epithelium (72 %, 28/39) and intralesional or intrauterine bacteria (66.5 %, 26/39) were identified in most animals. Bacterial isolates were obtained from 82 % (32/39) of the uterine contents and five bacterial species were identified. Escherichia coli, classified in phylogroup B2, is associated with virulent adhesion genes (fimH, focG, and papC), and serum resistance (traT) was the most common isolate. There was an association between the detection of papC in E. coli isolates and higher necrosis scores. Additionally, the necrosis score was positively associated with the length of hospitalization, with each point increase in the necrosis score leading to two more days of hospitalization. These results suggest that papC-positive E. coli play an important role in the severity of pyometra in dogs. The present study revealed the possibility of using this virulence gene to better understand the prognosis of the disease in an affected animal.

Central nervous system mycobacteriosis caused by Mycobacterium genavense in degus (Octodon degus).

Degus (Octodon degus) that were kept at a breeding facility presented with neurological or respiratory symptoms and died. Necropsies were performed on 9 individuals, and no significant gross lesions were found. Histologically, spinal cord necrosis was observed in all 9 cases and granulomatous myelitis in 5 of the 9 cases. Locally extensive necrosis of the brain and encephalitis were observed in 7 of the 9 cases. Acid-fast bacteria were found in the spinal cords, brains, and lungs from all 9 cases. Immunohistochemically, Mycobacterium tuberculosis antigen was observed in the spinal cords, brains, and lungs from all 9 cases. Double-labeling immunofluorescence revealed M. tuberculosis antigen in IBA1- and myeloperoxidase-immunopositive cells. Extracted genomic DNA from 8 of the 9 cases was successfully amplified with the primers for Mycobacterium genavense ITS1 and hypothetical 21 kDa protein genes, and the polymerase chain reaction products were identified as M. genavense by DNA sequencing. This report highlights the susceptibility of degus to M. genavense infection in the central nervous system.

Osteochondrosis in the central and third tarsal bones of young horses.

Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis.

Radiosynthesis of [18F]FPenM-C2Am: A PET Imaging Agent for Detecting Cell Death.

Imaging agents capable of detecting the extent, timing, and distribution of tumor cell death following treatment could be used in clinical trials of novel cancer therapies to get an early indication of efficacy and subsequently in the clinic to guide treatment in individual patients. We have shown how the C2A domain of synaptotagmin I, which binds the phosphatidylserine exposed by apoptotic and necrotic cells, can be used to image cell death (Bulat et al., EJNMMI Res 10(1):151, 2020; Neves et al. J Nucl Med 58(6):881-887, 2017). We describe here the semi-automated 18F labeling of the single cysteine residue in the protein (C2Am) that had been introduced by site-directed mutagenesis.

Molecular characterization and incidence of new tospovirus: Soybean Vein Necrosis Virus (SVNV) in Egypt / Caracterização molecular e incidência de novo tospovírus: Vírus da Necrose da Veia da Soja (SVNV) no Egito

Abstract Field survey study was conducted season (2017). Soybeans and weeds were weekly sampled randomly. Thrips adults were identified and counted. Detection of the virus isolate and the natural incidence was determined using; Mechanical transmission, host range, DAS-ELISA, RT-PCR. The natural incidence thrips individuals was detected depending on the SVNV% in thrips individuals and weeds hosts. Ten thrips species were associated with soybean plants in the field. The most abundant species was T. tabaci, average 256.5 average no.of individuals, followed by F. occidentalis (142.5 average no. of individuals), then N. variabilis (86.6/ average no. of individuals). Fourteen thrips species occurred on 5 legumes field crops and 41 weed plant species within soybean field. The highest average number 40.6.of individuals were recorded on Ammi majus. While the lowest one 3.3 average no. of individuals were on Urtica urens. Only 21diagnostic plant species were susceptible to infection with SVNV. G. max and Vigna radiate, were the highest percentage of infection 80% followed by V. unguilata & N. benthamiana, 75%. Egyptian isolate of Soybean vein necrosis virus (SVNV) in this study showed a high degree of similarity and it is closely related to TSWV from Egypt (DQ479968) and TCSV from USA (KY820965) with nucleotide sequence identity of 78%. Four thrips species transmitted SVNV (F. fusca 4.0%, F. schultzei 4.3%, F. tritici 3.3% and N. variabilis 68.0% transmission). Both C. phaseoli and M. sjostedti can acquire the virus but unable to transmit it. The following species; T. tabaci, F. occidentalis, S. dorsallis and T. palmi cannot acquire or transmit SVNV. The incidence of SVNV in the field started by the end of July then increased gradualy from 12.7 to 71.3% by the end of the season. In conclusion, few thrips individuals invaded soybean crops are enough to transmit high rate of SVNV within the crop. Furthermore, several vector species are also abundant on weeds, which are the major sources of soybean viruses transmitted to the crops. This information might be important for control and reduce the incidence of SVNV infection.

Resumo O estudo de pesquisa de campo foi realizado na temporada (2017). A soja e as ervas daninhas foram amostradas semanalmente de forma aleatória. Tripes adultos foram identificados e contados. A detecção do vírus isolado e a incidência natural foram determinadas usando transmissão mecânica, gama de hospedeiros, DAS-ELISA, RT-PCR. A incidência natural de tripes em indivíduos foi detectada dependendo da % de SVNV em tripes e hospedeiros infestantes. Dez espécies de tripes foram associadas a plantas de soja no campo. A espécie mais abundante foi T. tabaci, com média de 256,5 número médio de indivíduos, seguida por F. occidentalis (142,5) e N. variabilis (86,6 / número médio de indivíduos). Catorze espécies de tripes ocorreram em 5 culturas de leguminosas e 41 espécies de plantas daninhas dentro de campos de soja. O maior número médio de 40,6 indivíduos foi registrado em Ammi majus. Enquanto o mais baixo, 3,3 número médio de indivíduos, foi no Urtica urens. Apenas 21 espécies de plantas diagnosticadas foram suscetíveis à infecção com SVNV. G. max e Vigna radiate foram os maiores percentuais de infecção, 80%, seguidos por V. unguilata e N. benthamiana, 75%. O isolado egípcio neste estudo mostrou um alto grau de similaridade e está intimamente relacionado ao TSWV do Egito (DQ479968) e ao TCSV dos EUA (KY820965), com identidade de sequência de nucleotídeos de 78%. Quatro espécies de tripes transmitiram SVNV (F. fusca 4,0%, F. schultzei 4,3%, F. tritici 3,3% e N. variabilis 68,0% de transmissão). Tanto C. phaseoli quanto M. sjostedti podem adquirir o vírus, mas não podem transmiti-lo. As seguintes espécies, T. tabaci, F. occidentalis, S. dorsallis e T. palmi não podem adquirir ou transmitir SVNV. A incidência de SVNV no campo, iniciada no final de julho, aumentou gradativamente de 12,7 para 71,3% no final da temporada. Em conclusão, poucos indivíduos de tripes invadiram a cultura da soja e são suficientes para transmitir alta taxa de SVNV dentro da cultura. Além disso, várias espécies de vetores também abundam em ervas daninhas, que são as principais fontes dos vírus da soja transmitidos às lavouras. Essas informações podem ser importantes para controlar e reduzir a incidência de infecção por SVNV.

Isolation and Reproductive Structures Induction of Fungal Pathogens Associated with Xylem and Wood Necrosis in Grapevine.

Grapevine (Vitis vinifera L.) trunk diseases (GTDs) are considered a disease complex including five diseases: esca, Petri disease, black-foot disease, Botryosphaeria dieback, and Eutypa dieback. The main symptom is a general decline in affected plants, which show xylem necrosis and discoloration or sectorial necrosis in the wood. Their diagnosis is tedious due to four main reasons: (i) the wide diversity of internal symptoms that we can find; (ii) the great diversity of fungi that are associated with them; (iii) the high frequency of co-infections in the same plant; and (iv) the different behavior that the fungal species associated with GTDs show in vitro. Here, we describe a detailed protocol to isolate the different fungal trunk pathogens associated with GTDs as well as methods to induce sporulation and formation of fruiting bodies (pycnidia) to make easier their morphological characterization.

Can we preserve the necrotic testis caused by incarcerated inguinal hernia in infants under 3 months?

PURPOSE: This study aims to investigate whether necrotic testis resulting from incarcerated inguinal hernias can be preserved in infants under 3 months old. METHODS: A retrospective analysis was conducted on data collected from infants under 3 months old who had necrotic testis caused by incarcerated inguinal hernias between 2016 and 2020. They were divided into two groups: the orchiectomy group and the testicular preservation group. The control group consisted of normal male children of the same age. Data regarding bilateral testicular volume, dihydrotestosterone, inhibin B, and antisperm antibodies were collected. RESULTS: The study included 42 cases, with 18 patients being followed up for 6-54 months after the operation. In the testicular preservation group, 2 children did not experience testicular atrophy. There was no significant difference in the volume of the contralateral testes between the testicular preservation group and the control group; however, both groups had smaller testicular volumes compared to the orchiectomy group. There was no significant difference in the levels of inhibin B between the testicular preservation group and the orchiectomy group, although both were lower than the control group. Furthermore, no significant difference was observed in the levels of dihydrotestosterone and the positivity rate of antisperm antibodies among the three groups. CONCLUSION: Preserving the necrotic testis may allow it to survive without impacting the contralateral testis. Therefore, a more conservative approach should be considered for orchiectomy when dealing with testicular necrosis caused by incarcerated inguinal hernias in infants.

Dynamics of necroptosis in kidney ischemia-reperfusion injury.

Necroptosis, a pathway of regulated necrosis, involves recruitment and activation of RIPK1, RIPK3 and MLKL, leading to cell membrane rupture, cell death and release of intracellular contents causing further injury and inflammation. Necroptosis is believed to play an important role in the pathogenesis of kidney ischemia-reperfusion injury (IRI). However, the dynamics of necroptosis in kidney IRI is poorly understood, in part due to difficulties in detecting phosphorylated MLKL (pMLKL), the executioner of the necroptosis pathway. Here, we investigated the temporal and spatial activation of necroptosis in a mouse model of unilateral warm kidney IRI, using a robust method to stain pMLKL. We identified the period 3-12 hrs after reperfusion as a critical phase for the activation of necroptosis in proximal tubular cells. After 12 hrs, the predominant pattern of pMLKL staining shifted from cytoplasmic to membrane, indicating progression to the terminal phase of necroptotic cell death. Mlkl-ko mice exhibited reduced kidney inflammation at 12 hrs and lower serum creatinine and tubular injury at 24 hrs compared to wild-type littermates. Interestingly, we observed increased apoptosis in the injured kidneys of Mlkl-ko mice, suggesting a relationship between necroptosis and apoptosis in kidney IRI. Together, our findings confirm the role of necroptosis and necroinflammation in kidney IRI, and identify the first 3 hrs following reperfusion as a potential window for targeted treatments.

Assessing internal mammary lymph node metastasis by breast magnetic resonance imaging in breast cancer.

The internal mammary lymph nodes (IMLNs) are a main pathway of metastasis in breast cancer, and breast magnetic resonance imaging (MRI) plays an important role in staging that disease. We investigated the MRI parameters that can predict metastatic IMLNs and evaluated their diagnostic performance by comparing the breast MRI findings for metastatic and benign IMLNs. From January 2016 to December 2020, 474 cases of enlarged IMLNs on breast MRI were identified. By cytopathology or integrated positron emission tomography/computed tomography (PET/CT), 168 IMLNs were confirmed as metastatic, and 81 were confirmed as benign. Breast MRIs were reviewed by 2 radiologists, and various parameters (node axes, fatty hilum, necrosis, margin characteristics, restricted diffusion, and involved levels; primary tumor location and skin involvement) were assessed. Independent t-tests, receiver operating characteristic (ROC) curve analyses, chi-square tests, and Fisher exact tests were performed to compare and evaluate the diagnostic accuracy of the imaging findings. Significant differences in the breast MRI findings for the short and long axes, fatty hilum, necrosis, margin characteristics, diffusion restriction, and tumor location were observed between benign and metastatic IMLNs. Compared with the long axis and the ratio of the axes, the short axis had the best diagnostic value (higher area under the ROC curve) for predicting metastatic IMLNs. In conclusion, breast MRI parameters such as short axis, presence of fatty hilum, necrosis, margin characteristics, and diffusion restriction can be used to evaluate and differentiate benign from metastatic IMLNs, offering valuable insights to improve diagnosis and treatment planning in breast cancer.

Pathomorphological characteristics of tuberculous placenta and its clinical implication.

BACKGROUND: The study of pathologic diagnosis of placental TB is rare. The aim of this study is analyzing the pathomorphological characteristics of tuberculosis (TB) placenta during pregnancy and its clinical significance. METHODS: Nineteen cases of placental tissue specimens during pregnancy were collected from June 2015 to February 2022 at Shanghai Public Health Clinical Center, the only inpatient center for pregnant women with TB in Shanghai, China. Hematoxylin-eosin staining, acid-fast staining, and molecular testing were applied to analyze them comprehensively in combination with clinical information. RESULTS: Among the 19 cases, 7 cases caused intrauterine stillbirth, 3 cases received artificial abortion required by the pregnant woman, the other 9 cases received standard delivery and the infants survived, however, 3 of them were low-weight preterm infants, and another 1 case suffered mild intrauterine asphyxia. The 9 surviving infants were followed-up, of which 3 cases got congenital TB. For pathological characteristics of placental tissues under light microscopy, there were 3 cases of epithelioid granuloma formation, 13 cases of acute fetal membranitis, 4 cases of caseous necrosis, 7 cases of inflammatory necrosis, 10 cases of coagulative necrosis, and 6 cases with small focal calcifications. All placental tissues were positive for acid-fast staining and polymerase chain reaction (PCR). Molecular pathological diagnosis showed that 18 cases were positive for Mycobacterium tuberculosis, with 1 case not having received examination. CONCLUSIONS: Combining acid-fast staining and molecular pathological testing is helpful for accurately diagnosing placental TB.

[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

Growth factor free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.

Prooxidant effects of high dose ascorbic acid administration on biochemical, haematological and histological changes in Cavia porcellus (Guinea pigs): a Guinea pig experimental model.

Introduction: Ascorbic acid (AA) is a water-soluble vitamin that is well known for its antioxidant and immune-boosting properties. Owing to the wide-range application of AA in the treatment of numerous ailments and its sweet taste, it is usually abused i.e. overused. However, the effect of the abuse has rarely received attention. Therefore, this study was designed to assess the effect of oral administration of high-dose ascorbic acid on biochemical and haematological parameters as well as the effects on the kidney, liver and lungs. Methods: adult guinea pigs were divided into four (4) groups where group 1 served as the untreated control group and groups 2-4 were dosed with 29 mg, 662 mg and 1258 mg of ascorbic acid per day, respectively for 28 days. Results: the result revealed that administration of high dose ascorbic acid significantly (P<0.05) increased serum creatinine from 50.0 ± 7.09 (NC) to AA29- 73.8 ± 4.5, AA-662-89.7 ± 3.3 and AA1258- 79.9 ± 5.7mmol/L and urea levels in the treatment group AA-1258 -18.3 ± 0.5 µmol/L compared to the normal group (NC-2.15 ± 0.6 µmol/L). Disturbance in electrolyte balance was observed with a significant (P<0.05) increase in Na+ from NC- 131.3 ± 3.5 mmol/L to 135.7 ± 3.6 mmol/L in the AA-1258 treatment group, Cl- ( NC- 67.1 ± 1.6 mmol/L increased to AA29- 92.1 ± 0.83, AA662- 95.3 ± 1.3 and AA-1258- 95.6 ± 0.4 mmol/L), and Ca2+ (NC- 2.66 ± 0.03 to AA1258- 3.36 ± 0.03 mmol/L) and a significant (P<0.05) decrease in serum K+ in the AA29-5.0 ± 0.2, AA662-5.2 ± 0.3 and AA1258-5.6 ± 0.3 mmol/L treatment groups compared to the normal group 6.6 ± 0.3 mmol/L. There was also a significant (P<0.05) increase in the differential blood count in the animals with a significant (P<0.05) increase in red blood count ( NC-5.11 ± 0.13 ×106/µL to AA1258- 5.75 ± 0.11×106/µL ), haematocrit count (NC 39.90 ± 0.52% to AA-29-42.08 ± 0.24 and AA1258-46.13 ± 0.86%), white blood count (NC 10.15 ± 1.01 ×103/µL to AA1258- 15.18 ± 1.65×103/µL ), total lymphocytes (NC 3.5 ± 0.51×103/µL to AA29-5.28 ±0.43×103/µL), monocytes (NC 0.45 ± 0.07×103/µL to AA1258 0.80 ± 0.07×103/µL), eosinophils (NC 0.23 ± 0.03×103/µL to AA12580.40 ± 0.03×103/µL), basophils (NC0.68 ± 0.10×103/µL to AA12581.20 ± 0.10×103/µL) and neutrophil count (NC 4.73 ± 0.68×103/µL to AA1258 8.36 ± 0.71×103/µL). The histopathological indices indicate cellular necrosis in the AA662 and AA1258 treatment groups of the kidney and liver respectively compared to the normal control which has normal cells. Conclusion: high dose of ascorbic acid can therefore be suggested to cause damage to the cells by causing cellular necrosis as observed in the histopathology results and has effect on the blood cells as observed in the increase compared to the normal control, and the consequences are possibly triggered through inflammatory responses.

[One case of bromadiolone poisoning leading to intestinal necrosis and severe coagulopathy].

Bromadiolone is still often used in life as a poisonous rodent agent. Bromadiolone poisoning is often manifested as coagulation dysfunction, resulting in organ bleeding, including cerebral hemorrhage, intestinal bleeding, abdominal hemorrhage, etc. At present, no case of intestinal necrosis caused by bromadiolone poisoning have been reported. This article reviewed one case of intestinal necrosis and severe coagulation dysfunction, and finally confirmed bromadiolone poisoning by poison detection. The patient recovered and was discharged after surgery, vitamin K injection, plasma transfusion and other treatment methods.

Diagnostic Value Analysis of Multi-Slice Helical Computed Tomography Reconstruction Parameters Combined with 3.0 T Magnetic Resonance in Clear Cell Renal Cell Carcinoma.

OBJECTIVE: The diagnostic value of multi-slice helical computed tomography (MSCT) reconstruction parameters combined with 3.0 T magnetic resonance (MR) in clear cell renal cell carcinoma (CCRCC) was analysed. METHODS: A total of 158 patients with renal tumours were selected in First Hospital in Zibo city from February 2018 to March 2023 for the retrospective study and divided into CCRCC and non-CCRCCs groups according to the final results of pathological diagnosis. MSCT detection and 3.0 T MR detection were performed in both groups for imaging manifestation analysis. The receiver operating characteristic (ROC) curve was used in analysing the clinical efficacy of each single and combined diagnosis. RESULTS: The results of pathological diagnosis showed 115 patients with CCRCC and 43 non-CCRCC patients, accounting for 72.78% and 27.22%, respectively. Patients with CCRCC had higher proportions of calcification, necrosis, cystic degeneration and more pseudocapsules than non-CCRCC patients (p < 0.05). Patients with CCRCC mainly showed peripheral and heterogeneous enhancement, whereas non-CCRCC patients mainly showed homogeneous enhancement, and the difference was significant (p < 0.05). The cortical phase, parenchymal phase and excretion stage had higher computed tomography (CT) values in the CCRCC group (p < 0.001), and no significant difference in the CT value of plain scan phase was found between the groups (p > 0.05). The CCRCC group had obviously higher apparent diffusion coefficient value and incidence of necrosis and cystic degeneration (p < 0.001), lower incidence of haemorrhage (p < 0.05) and distinctly higher cortical enhancement indexes in the cortical phase, parenchymal phase and delay period (p < 0.001). The ROC analysis showed that the area under the curve, specificity, sensitivity and 95% CI of combined detection were higher than those of each single detection. CONCLUSIONS: The combination of MSCT reconstruction parameters and 3.0 T MR has a certain diagnostic value for CCRCC. The combined diagnosis has higher area under the curve, specificity, sensitivity and 95% CI, which can provide effective reference for clinical diagnosis and treatment, with a certain clinical application value.

Extensive arm skin necrosis following administration of unfractionated heparin.

Unfractionated heparin (UH), a commonly used anticoagulant, can rarely cause skin necrosis following heparin-induced thrombocytopenia (HIT). A 38-year-old female, a case of chronic inflammatory demyelinating polyneuropathy (CIDP) admitted to the neurology ward, developed extensive skin necrosis following a change in UH dose at the exact site of UH injection. A sudden fall in the platelet count was observed within 48 h of increasing the UH dose. Necrosis of the outer layer of the skin along with clot formation and inflammation in the inner layers was detected after histopathological evaluation. UH was discontinued, and rivaroxaban was started for the patient as soon as the complication was detected. The patient was discharged in good condition after completing treatment for CIDP without any need for surgical removal of the necrotic tissue. Extensive skin necrosis, as a result of HIT, requires immediate discontinuation of UH and substitution of a nonheparin-based anticoagulation treatment.