外伤性晶状体脱位合并周边隐匿性视网膜病变的临床特征及预后分析

目的观察分析眼球钝挫伤合并外伤性晶状体脱位患者周边隐匿性视网膜病变的临床特点及预后。 方法本研究纳入2013年1月至2020年1月在柳州市人民医院眼科住院诊断为眼球钝挫伤合并外伤性晶状体脱位，并行23G微创玻璃体切割联合白内障摘除手术的72例（72眼）患者。根据裂隙灯和超声生物显微镜（UBM）检查，将患者分为晶状体不全脱位组和全脱位组，详细记录2组患者的术中周边视网膜病变情况，并分析其临床特征及疗效。 结果眼球钝挫伤合并外伤性晶状体脱位患者中有周边隐匿性视网膜病变的占72.22%，其中晶状体不全脱位组发生率高达80.95%，显著大于晶状体全脱位组的60.00%（P＜0.05）。2组患者的周边隐匿性视网膜病变均以隐匿性视网膜裂孔、变性和出血为最常见。所有患者术后视网膜情况稳定，视力预后较好。 结论眼球钝挫伤合并外伤性晶状体脱位患者常出现周边隐匿性视网膜病变，最常见的是视网膜裂孔、出血、变性。23G微创玻璃体切割联合白内障摘除手术是有效治疗手段，具有创伤小、并发症少的优势。     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

BCL2 G quadruplex-binding small molecules: Current status and prospects for the development of next-generation anticancer therapeutics

B cell lymphoma 2 (BCL2) overexpression in a range of human tumors is often related to chemotherapy resistance and poor prognosis. GC-rich regions upstream of the P1 promoter in human BCL2 can form G-quadruplex (G4) structures through the stacking of four Hoogsteen-paired guanine bases. Stabilizing the G4 fold implies the inhibition of BCL2 expression and, thus, small molecules that selectively bind to the G4 are promising anticancer candidates. In this review, we discuss the structural aspects, binding affinity, selectivity, and biological activity of well-characterized BCL2 G4 binding ligands in vitro and in vivo. We also explore future directions in the research and development of G4-based anticancer therapeutics.     

A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Exon1 and -116 C/G Promoter Polymorphism on the X-Box DNA Binding Protein- 1 Gene is not Associated with Breast Cancer among Jordanian Women

Background: Human X -box binding protein 1 (XBP1), a critical gene in the endoplasmic reticulum stress response, islocated on chromosome 22q12, which has been linked with the pathogenesis of many diseases, particularly cancers suchas breast cancer (BC). Single nucleotide polymorphisms (SNPs) in the XBP1 gene can alter structure and function of thegene. In this study, polymorphism in the promoter region and exon1 of the gene XBP1 and its association with BCin Jordanian women was investigated. Methods: Polymorphism in the promoter and exon1 of XBP1 was analyzedin 100 subjects (controls: n=40; BC patients=60). −116 C/G SNP was genotyped by Polymerase Chain Reaction(PCR)-sequence specific primer technique. The odd ratios (ORs) at 95% confidence intervals (CIs) were computedto assess the strength of this association. Results: The three genotypes of the SNP (GG, GC, CC) and their allelicfrequencies have nonsignificant differences between patients and control group. It was noticed that the frequencies ofthe mutant allele (G) were (75.8% versus 24.2%)) in the patients and control groups, respectively, while those of thenormal allele (C) were (67.5% versus 32.5%). XBP1 (-116 G→C) G allele did not show significant association withBC risk (confidence interval = 0.3534- 1.2395, odds ratio = 0.6619, P= 0.197). Moreover, there were no significantmutations in the XBP1 exon1 neither in BC subjects nor control subjects. Conclusions: This is the first study to evaluatethe effect of polymorphism in the promoter and exon1 of XBP1 gene in the pathogenesis of BC in Jordanian women.The results do not support a role for polymorphism in development of BC and further studies with a larger sample sizeand detailed data should be performed in other populations.     

Gi/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission

G protein-coupled receptors (GPCRs) play key roles in intercellular signaling in the brain. Their effects on cellular function have been largely studied in neurons, but their functional consequences on astrocytes are less known. Using both endogenous and chemogenetic approaches with DREADDs, we have investigated the effects of G_q and G_i/o GPCR activation on astroglial Ca²⁺-based activity, gliotransmitter release, and the functional consequences on neuronal electrical activity. We found that while G_qGPCR activation led to cellular activation in both neurons and astrocytes, G_i/oGPCR activation led to cellular inhibition in neurons and cellular activation in astrocytes. Astroglial activation by either G_q or G_i/o protein-mediated signaling stimulated gliotransmitter release, which increased neuronal excitability. Additionally, activation of G_q and G_i/o DREADDs in vivo increased astrocyte Ca²⁺ activity and modified neuronal network electrical activity. Present results reveal additional complexity of the signaling consequences of excitatory and inhibitory neurotransmitters in astroglia-neuron network operation and brain function.