[Diagnostic Value of Ultrasound for Thyroid Nodules With a Spoke-Wheel Blood Flow Pattern].

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (χ2=5.968,P=0.015),while central coarse calcification was more common in benign nodules (χ2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both P<0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

Influence of Ocular Biometric Parameters on Intraocular Lens Position: A Prospective Cohort Study.

PURPOSE: To assess the influence of ocular biometric parameters on intraocular lens (IOL) tilt and decentration after cataract surgery. METHODS: Patients scheduled for cataract surgery were screened for inclusion in this prospective cohort study. Tilt and decentration of the crystalline lens and IOL were measured using the CASIA2 (Tomey). Anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) were preoperatively measured by the IOLMaster 700 (Carl Zeiss Meditec AG). Multivariate regression analysis was performed to assess the influence of ocular biometric parameters on IOL tilt and decentration after cataract surgery. RESULTS: In total, 191 eyes of 120 patients were included. Age was positively correlated with IOL tilt, whereas ACD and AL were negatively correlated with IOL tilt. A strong positive correlation was found between preoperative crystalline lenses and postoperative IOLs in tilt magnitude (r = 0.769, P < .001) and tilt direction (r = 0.688, P < .001). A positive correlation was found between preoperative and postoperative lens decentration magnitude and decentration direction. Greater postoperative IOL tilt and decentration were significantly associated with greater preoperative crystalline lens tilt (P < .001) and decentration (P = .027). CONCLUSIONS: IOL tilt was greater in older patients. Shorter AL and shallower ACD contributed to greater IOL tilt. The tilt and decentration of the IOL will be greater in patients with greater tilt and decentration of the crystalline lens. [J Refract Surg. 2024;40(7):e438-e444.].

Toxoplasma gondii infection supports the infiltration of T cells into brain tumors.

Few T cells infiltrate into primary brain tumors, fundamentally hampering the effectiveness of immunotherapy. We hypothesized that Toxoplasma gondii, a microorganism that naturally elicits a Th1 response in the brain, can promote T cell infiltration into brain tumors despite their immune suppressive microenvironment. Using a mouse genetic model for medulloblastoma, we found that T. gondii infection induced the infiltration of activatable T cells into the tumor mass and led to myeloid cell reprogramming toward a T cell-supportive state, without causing severe health issues in mice. The study provides a concrete foundation for future studies to take advantage of the immune modulatory capacity of T. gondii to facilitate brain tumor immunotherapy.

iNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse.

Toxoplasma gondii is an obligate intracellular parasite of rodents and humans. Interferon-inducible guanylate binding proteins (GBPs) are mediators of T. gondii clearance, however, this mechanism is incomplete. Here, using automated spatially targeted optical micro proteomics we demonstrate that inducible nitric oxide synthetase (iNOS) is highly enriched at GBP2+ parasitophorous vacuoles (PV) in murine macrophages. iNOS expression in macrophages is necessary to limit T. gondii load in vivo and in vitro. Although iNOS activity is dispensable for GBP2 recruitment and PV membrane ruffling; parasites can replicate, egress and shed GBP2 when iNOS is inhibited. T. gondii clearance by iNOS requires nitric oxide, leading to nitration of the PV and collapse of the intravacuolar network of membranes in a chromosome 3 GBP-dependent manner. We conclude that reactive nitrogen species generated by iNOS cooperate with GBPs to target distinct structures in the PV that are necessary for optimal parasite clearance in macrophages.

Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated in T. gondii infection-induced cachexia.

Cachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasite Toxoplasma gondii represent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, non-esterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice with T. gondii infection-induced cachexia. In addition, the TCA cycle intermediates α-ketoglutarate, 2-hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance driving T. gondii-induced chronic cachexia.

Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging.

Mitochondrial dysfunction is linked to age-associated inflammation or inflammaging, but underlying mechanisms are not understood. Analyses of 700 human blood transcriptomes revealed clear signs of age-associated low-grade inflammation. Among changes in mitochondrial components, we found that the expression of mitochondrial calcium uniporter (MCU) and its regulatory subunit MICU1, genes central to mitochondrial Ca2+ (mCa2+) signaling, correlated inversely with age. Indeed, mCa2+ uptake capacity of mouse macrophages decreased significantly with age. We show that in both human and mouse macrophages, reduced mCa2+ uptake amplifies cytosolic Ca2+ oscillations and potentiates downstream nuclear factor kappa B activation, which is central to inflammation. Our findings pinpoint the mitochondrial calcium uniporter complex as a keystone molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation. The findings raise the exciting possibility that restoring mCa2+ uptake capacity in tissue-resident macrophages may decrease inflammaging of specific organs and alleviate age-associated conditions such as neurodegenerative and cardiometabolic diseases.

Integrative Analysis of Minichromosome Maintenance Proteins and Their Prognostic Significance in Melanoma.

BACKGROUND: Minichromosome maintenance (MCM) is known for participating in cell cycle progression, as well as DNA replication. While the diverse expression patterns and prognostic values of MCMs in melanoma still remained unclear. METHODS: In the present study, the transcriptional and clinical profiles of MCMs were explored in patients with melanoma from multiple databases, including GEO, TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, and TIMER databases. RESULTS: We found that the elevated expressions of MCM2-6 and MCM10 were significantly expressed in melanoma compared to normal skin. High mRNA levels of MCM4, MCM5, and MCM10 were closely related to worse prognosis in patients with melanoma. GSEA showed hallmark pathways were most involved in mTORC1 signaling, G2M checkpoint, E2F targets, and mitotic spindle. Furthermore, we found potential correlations between the MCM expression and the immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. CONCLUSION: Upregulated MCM gene expression in melanoma probably played a crucial part in the development and progression of melanoma. The upregulated MCM4/5/10 expressions could be used as potential prognostic markers to improve the poor outcome and prognostic accuracy in patients with melanoma. Our study might shed light on the selection of prognostic biomarkers as well as the underlying molecular pathogenesis of melanoma.

The Effect of Inclusions on a Medium Temperature Transformation Microstructure and Toughness of High-Strength HSLA Steel.

In this study, the evolution of high-strength HSLA steel microstructure was studied using high-temperature laser confocal microscopy and SEM, TEM, and EPMA techniques. The effect of precipitates on grain boundary migration of austenite during high-temperature heating and the effect of inclusions in undercooled austenite on AF phase transformation were studied. The effect of multiphase microstructure on impact toughness was studied by Gleeble thermal simulation at 550, 600, and 650 °C. The results show that the austenite grain is refined by TiN pinning at high temperatures, and a large number of NbC and VCN are precipitated in ferrite for precipitation strengthening. The (Ti-Mn-O) + (Al + Si + Mn-O) + MnS composite inclusions with smaller sizes have a greater promoting effect on the nucleation of acicular ferrite than single-phase MnS. With a decrease in isothermal temperature, the content of acicular ferrite increases. When the isothermal temperature is 550 °C, an increase in the maximum impact toughness of acicular ferrite with large-angle grain boundary is clearly observable.

Data mining of immune-related prognostic genes in metastatic melanoma microenvironment.

Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein-protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma.

Identification, Validation, and Functional Annotations of Genome-Wide Profile Variation between Melanocytic Nevus and Malignant Melanoma.

Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, including FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2, were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevated FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the P53 pathway, K-ras signaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma.

Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation for adenomyosis: preliminary results.

Purpose: Adenomyosis is a relatively common disease among women of childbearing age. A minimally invasive alternative technique with low risks, faster recovery and decreased side effects is desired. We hypothesized that percutaneous microwave ablation (PMWA) under laparoscopic guidance would substantially reduce the risk of collateral thermal damage to the intestinal tract and relieve the pelvic adhesions. This study aimed to evaluate the feasibility, safety and efficacy of transvaginal ultrasound- and laparoscopy-guided PMWA for the treatment of adenomyosis.Materials and methods: From May 2015 to October 2017, a total of 70 patients with symptomatic adenomyosis who underwent transvaginal ultrasound- and laparoscopy-guided PMWA were included in this study. The technical efficacy and complications of PMWA were assessed. Meanwhile, the uterine volume, lesion volume, symptom severity score (SSS) and visual analog scale (VAS) score before PMWA and at 1, 6 and 12 months after PMWA were recorded.Results: PMWA was successfully performed with transvaginal ultrasound guidance and laparoscope assistance in all patients. No major complication was found after PMWA in any patients. The uterine volume, lesion volume, SSS and VAS were all decreased significantly at follow-up (p < .01).Conclusion: Transvaginal ultrasound- and laparoscopy-guided PMWA, which significantly decreased the uterine volume, lesion volume, SSS and VAS score, is a feasible minimally invasive technique for the treatment of adenomyosis.

Okadaic acid (OA): Toxicity, detection and detoxification.

Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after ingestion of contaminated shellfish. In vivo and in vitro studies have revealed that exposure of various cells, including human embryonic amniotic cells, hepatocytes, neuroblastoma cells, to OA induces morphological and functional modifications as well as the death of cells. As the number of reports on OA poisoning has increased, this toxin has gradually attracted the public's attention, and researchers are trying to study it. This review summarizes the current literature on the toxicity effects of OA, in addition to its detection and detoxification.

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression.

UNLABELLED: B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defined by their ability to produce IL10 downregulate inflammation and control T-cell immunity. Here, we identified a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼10% of all B cells in advanced-stage hepatocellular carcinoma (HCC). These PD-1(hi) B cells exhibited a unique CD5(hi)CD24(-/+)CD27(hi/+)CD38(dim) phenotype different from the phenotype of conventional CD24(hi)CD38(hi) peripheral regulatory B cells. TLR4-mediated BCL6 upregulation was crucial for PD-1(hi) B-cell induction by HCC environmental factors, and that effect was abolished by IL4-elicited STAT6 phosphorylation. Importantly, upon encountering PD-L1(+) cells or undergoing PD-1 triggering, PD-1(hi) B cells acquired regulatory functions that suppressed tumor-specific T-cell immunity and promoted cancer growth via IL10 signals. Our findings provide significant new insights for human cancer immunosuppression and anticancer therapies regarding PD-1/PD-L1. SIGNIFICANCE: We identify a novel protumorigenic PD-1(hi) B-cell subset in human HCC that exhibits a phenotype distinct from that of peripheral regulatory B cells. TLR4-mediated BCL6 upregulation is critical for induction of PD-1(hi) B cells, which operate via IL10-dependent pathways upon interacting with PD-L1 to cause T-cell dysfunction and foster disease progression. Cancer Discov; 6(5); 546-59. ©2016 AACR.See related commentary by Ren et al., p. 477This article is highlighted in the In This Issue feature, p. 461.

Repairing Facial Soft Tissue Defects by Swelling Anesthesia after Tumor Resection with Narrow Pedicle Flaps.

AIMS: To investigate the role of swelling anesthesia in repairing facial soft tissue defects after tumor resection and temporal superficial artery frontal branch of narrow pedicle flap. MATERIALS AND METHODS: From January 2008 to June 2008, 16 patients from Department of Ophthalmology with eye or eyelid tumors after eyeball removal of eye and part resection of surrounding soft tissue, undergoing postoperative swelling anesthesia with superficial temporal artery flap repair to prevent facial soft tissue defect formation and bone exposure, were recruited. RESULTS: In all 16 patients facial soft tissue defect repair had good effects, with limited bleeding, and short operation times. Seven days after surgery, all flaps were in good repair. On postoperative follow-up after 3 months, flaps showed a similar appearance as with facial tissue. CONCLUSIONS: Swelling anesthesia for superficial temporoparietal artery frontal branch of narrow pedicle flap to repair soft tissue defect after facial tumor resection is feasible, and is linked with good analgesic effects, high postoperative survival of skin flaps, and good cosmetic effects.

Chemokine (C-X-C motif) receptor 3-positive B cells link interleukin-17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma.

UNLABELLED: B cells consistently represent abundant cellular components in tumors; however, direct evidence supporting a role for B cells in the immunopathogenesis of human cancers is lacking, as is specific knowledge of their trafficking mechanisms. Here, we demonstrate that chemokine (C-X-C motif) receptor 3-positive (CXCR3(+)) B cells constitute approximately 45% of B-cell infiltrate in human hepatocellular carcinoma (HCC) and that their levels are positively correlated with early recurrence of HCC. These cells selectively accumulate at the invading edge of HCC and undergo further somatic hypermutation and immunoglobulin G-secreting plasma cell differentiation. Proinflammatory interleukin-17(+) cells are important for the induction of epithelial cell-derived CXCR3 ligands CXCL9, CXCL10, and CXCL11, which subsequently promote the sequential recruitment and further maturation of CXCR3(+) B cells. More importantly, we provide evidence that CXCR3(+) B cells, but not their CXCR3(-) counterparts, may operate in immunoglobulin G-dependent pathways to induce M2b macrophage polarization in human HCC. Depletion of B cells significantly suppresses M2b polarization and the protumorigenic activity of tumor-associated macrophages and restores the production of antitumorigenic interleukin-12 by those cells in vivo. CONCLUSION: Selective recruitment of CXCR3(+) B cells bridges proinflammatory interleukin-17 response and protumorigenic macrophage polarization in the tumor milieu, and blocking CXCR3(+) B-cell migration or function may help defeat HCC.

Immune reconstitution after haploidentical hematopoietic stem cell transplantation.

Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely HLA-matched sibling or who require urgent transplantation. Unfortunately, serious infections and leukemia relapse resulting from slow immune reconstitution remain the 2 most frequent causes of mortality in patients undergoing haploidentical HSCT, particularly in those receiving extensively T cell-depleted megadose CD34(+) allografts. This review summarizes advances in immune recovery after haploidentical HSCT, focusing on the immune subsets likely to have the greatest impact on clinical outcomes. The progress made in accelerating immune reconstitution using different strategies after haploidentical HSCT is also discussed. It is our belief that a predictive immune subset-guided strategy to improve immune recovery might represent a future clinical direction.

[Meta analysis on etiological relationship between human papillomavirus and esophageal carcinoma].

OBJECTIVE: To study the relationship between human papillomavirus (HPV) and esophageal cancer development in China. METHODS: We searched and collected the published articles in Chinese related to HPV and esophageal cancer, and selected the articles with the PCR approach to detect HPV in the esophageal cancer specimens. RESULTS: We filtered our publication collection with standards as (1) PCR as the detection approach, (2) specimens as the paraffin-embedded sections, and (3) description of the primer in the experiments, and fifteen articles were enrolled for our meta-analysis. Among the articles, totally 980 specimens were tested, and 460 were HPV positive with the average HPV prevalence was 46.9% (95% CI: 43.8%-50.0%), varied from 8.3%-69.8% in the different locations. On the other hands, among 556 specimens whose HPV detection spectrum included HPV16, 139 showed the positivity of HPV16, the average prevalence was 25.0%, (95% CI: 21.4%-28.6%) varied from 4.4%-63.4% dependent on the locations; among 485 specimens whose HPV detection spectrum included HPV18, thirty-three specimens showed the positivity of HPV18, the average prevalence was 6.8% (95% CI: 4.6%-9.0%) varied from 0%-19.0% dependent on the locations. Third, among the fifteen articles enrolled in the meta-analysis, four articles used the same primer set for HPV detection in totally 406 paraffin-embedded specimens with the prevalence of 40.2% (95% CI: 36.0%-45.4%) varied from 20.3%-67.6% in different locations. CONCLUSION: Our analysis result suggested the HPV prevalence in the esophageal cancer samples of China and clued the possible etiological relationships between HPV infection and the esophageal cancer development.

[Detection of human papillomavirus in esophageal carcinoma tissues from Baoding City of Hebei Province].

OBJECTIVE: To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinoma in Baoding City of Hebei Province. METHODS: We detected HPV DNA in 42 formalin-fixed and paraffin-embedded tissues from surgically resected esophageal carcinomas from Baoding City of Hebei Province, by PCR with the general primer set of GP5 + /6 + for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well. RESULTS: 37 from 42 esophageal carcinoma samples were HPV positive and the rate was 88.1%. Among the samples detected, 19 were HPV16 E6 positive and rate was 45.2%, eight were HPV18 E6 positive and rate was 19.0%. CONCLUSION: The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Baoding City of Hebei Province.

[Detection of human papillomavirus in tissues of esophageal carcinomas by polymerase chain reaction].

OBJECTIVE: To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinomas. METHODS: We detected HPV DNA in 31 fresh tissue of esophageal carcinomas from Linzhou City, Henan Province, by PCR with the general primer set of GP5+/6+ for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well. RESULTS: 29 from 31 esophageal carcinoma samples were HPV positive and the rate was 93.5%. Among the samples detected, 19 were HPV16E6 positive and rate was 61.3%, eight were HPV18 E6 positive and rate was 25.8%; our result also showed five were the multiple infection containing HPV16 and 18 as well and the rate was 71.0%. CONCLUSION: The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Linzhou City, Henan Province.

[Suppressive effect of rhIL-24 protein on the human A375 cell melanoma in nude mouse].

OBJECTIVE: To study the suppressive effect of purified and renaturalized rhIL-24 protein on the human A375 cell melanoma in nude mouse. METHODS: Human A375 cells were injected into the nude mouse. After the volume of tumor attained, rhIL-24 was injected into the tumor. 2 weeks later, the tumors were resected for measurement of volume and weight, following with pathological and immunohistochemistry examination. RESULTS: The volume and weight of tumors were decreased markedly after treatment of rhIL-24, when compared with those in controls. The expression of Bax gene upregulated, while Bcl-2, CD34 and VEGF gene downregulated. It indicated tumor growth inhibition and inducing of apoptosis of tumor cells. CONCLUSIONS: rhIL-24 has a suppressive effect on the A375 cell melanoma in nude mouse. It can also induce the A375 cell apoptosis without side effect on nude mouse.