Comparative assessment of the capability of machine learning-based radiomic models for predicting omental metastasis in locally advanced gastric cancer.

The study aims to investigate the predictive capability of machine learning algorithms for omental metastasis in locally advanced gastric cancer (LAGC) and to compare the performance metrics of various machine learning predictive models. A retrospective collection of 478 pathologically confirmed LAGC patients was undertaken, encompassing both clinical features and arterial phase computed tomography images. Radiomic features were extracted using 3D Slicer software. Clinical and radiomic features were further filtered through lasso regression. Selected clinical and radiomic features were used to construct omental metastasis predictive models using support vector machine (SVM), decision tree (DT), random forest (RF), K-nearest neighbors (KNN), and logistic regression (LR). The models' performance metrics included accuracy, area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In the training cohort, the RF predictive model surpassed LR, SVM, DT, and KNN in terms of accuracy, AUC, sensitivity, specificity, PPV, and NPV. Compared to the other four predictive models, the RF model significantly improved PPV. In the test cohort, all five machine learning predictive models exhibited lower PPVs. The DT model demonstrated the most significant variation in performance metrics relative to the other models, with a sensitivity of 0.231 and specificity of 0.990. The LR-based predictive model had the lowest PPV at 0.210, compared to the other four models. In the external validation cohort, the performance metrics of the predictive models were generally consistent with those in the test cohort. The LR-based model for predicting omental metastasis exhibited a lower PPV. Among the machine learning algorithms, the RF predictive model demonstrated higher accuracy and improved PPV relative to LR, SVM, KNN, and DT models.

Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.

Osteosarcoma is the most common malignant bone tumor. It has a poor prognosis because of a lack of therapeutic targets and strategies. The SET domain-containing lysine-specific methyltransferase, SET7/9, has various functions in different cancer types in tissue-type and signaling context-dependent manners. The role of SET7/9 in osteosarcoma cells is currently controversial and its potential as a therapeutic candidate in osteosarcoma is unknown. In the present study, SET7/9 inhibition or ablation suppressed osteosarcoma cell proliferation by causing G1 arrest. Mechanistically, SET7/9 inhibition disrupted the interaction between cyclin-dependent kinase 4 (CDK4) and cyclin D1, which affected CDK4-cyclin D1 complex function, leading to decreased phosphorylation of retinoblastoma protein. CDK4 was overexpressed in osteosarcoma tissues and was closely related to a poor prognosis in patients with osteosarcoma. We therefore hypothesized that SET7/9 inhibition might increase the sensitivity of osteosarcoma cells to CDK4 inhibitors, potentially decreasing the risk of adverse effects of CDK4 inhibitors. The combination of SET7/9 and CDK4 inhibition enabled dose reductions of both inhibitors and had a synergistic effect against osteosarcoma growth in vivo. Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.

Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Hub gene identification and molecular subtype construction for Helicobacter pylori in gastric cancer via machine learning methods and NMF algorithm.

Helicobacter pylori (HP) is a gram-negative and spiral-shaped bacterium colonizing the human stomach and has been recognized as the risk factor of gastritis, peptic ulcer disease, and gastric cancer (GC). Moreover, it was recently identified as a class I carcinogen, which affects the occurrence and progression of GC via inducing various oncogenic pathways. Therefore, identifying the HP-related key genes is crucial for understanding the oncogenic mechanisms and improving the outcomes of GC patients. We retrieved the list of HP-related gene sets from the Molecular Signatures Database. Based on the HP-related genes, unsupervised non-negative matrix factorization (NMF) clustering method was conducted to stratify TCGA-STAD, GSE15459, GSE84433 samples into two clusters with distinct clinical outcomes and immune infiltration characterization. Subsequently, two machine learning (ML) strategies, including support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), were employed to determine twelve hub HP-related genes. Beyond that, receiver operating characteristic and Kaplan-Meier curves further confirmed the diagnostic value and prognostic significance of hub genes. Finally, expression of HP-related hub genes was tested by qRT-PCR array and immunohistochemical images. Additionally, functional pathway enrichment analysis indicated that these hub genes were implicated in the genesis and progression of GC by activating or inhibiting the classical cancer-associated pathways, such as epithelial-mesenchymal transition, cell cycle, apoptosis, RAS/MAPK, etc. In the present study, we constructed a novel HP-related tumor classification in different datasets, and screened out twelve hub genes via performing the ML algorithms, which may contribute to the molecular diagnosis and personalized therapy of GC.

Development and validation of nomograms predicting overall and cancer-specific survival for non-metastatic primary malignant bone tumor of spine patients.

At present, no study has established a survival prediction model for non-metastatic primary malignant bone tumors of the spine (PMBS) patients. The clinical features and prognostic limitations of PMBS patients still require further exploration. Data on patients with non-metastatic PBMS from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression analysis using Cox, Best-subset and Lasso regression methods was performed to identify the best combination of independent predictors. Then two nomograms were structured based on these factors for overall survival (OS) and cancer-specific survival (CSS). The accuracy and applicability of the nomograms were assessed by area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Results: The C-index indicated that the nomograms of OS (C-index 0.753) and CSS (C-index 0.812) had good discriminative power. The calibration curve displays a great match between the model's predictions and actual observations. DCA curves show our models for OS (range: 0.09-0.741) and CSS (range: 0.075-0.580) have clinical value within a specific threshold probability range compared with the two extreme cases. Two nomograms and web-based survival calculators based on established clinical characteristics was developed for OS and CSS. These can provide a reference for clinicians to formulate treatment plans for patients.

Surgical treatment versus observation in moderate intermittent exotropia (SOMIX): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent exotropia (IXT) is the most common type of strabismus in China, but the best treatment and optimal timing of intervention for IXT remain controversial, particularly for children with moderate IXT who manifest obvious exodeviation frequently but with only partial impairment of binocular single vision. The lack of randomized controlled trial (RCT) evidence means that the true effectiveness of the surgical treatment in curing moderate IXT is still unknown. The SOMIX (surgical treatment versus observation in moderate intermittent exotropia) study has been designed to determine the long-term effectiveness of surgery for the treatment and the natural history of IXT among patients aged 5 to 18 years old. METHODS/DESIGN: A total of 280 patients between 5 and 18 years of age with moderate IXT will be enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. After initial clinical assessment, all participants will be randomized to receive surgical treatment or observation, and then be followed up for 5 years. The primary objective is to compare the cure rate of IXT between the surgical treatment and observation group. The secondary objectives are to identify the predictive factors affecting long-term outcomes in each group and to observe the natural course of IXT. DISCUSSION: The SOMIX trial will provide important guidance regarding the moderate IXT and its managements and modify the treatment strategies of IXT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02736526 . Registered April 13, 2016.

Echinacoside from Cistanche tubulosa ameliorates alcohol-induced liver injury and oxidative stress by targeting Nrf2.

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong-Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti-inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2-related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML-12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase-3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol-induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.

Verbenalin attenuates hepatic damage and mitochondrial dysfunction in alcohol-associated steatohepatitis by regulating MDMX/PPARα-mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbenalin is a major compound in Verbena officinalis L. Verbena officinalis L was first recorded in the 'Supplementary Records of Famous Physicians.' Verbenalin (VE) is its active constituent and has been found to have many biological effects, including anti-obesity, anti-inflammatory, and antioxidant activities, removing jaundice, and treating malaria. It could treat lump accumulation, dysmenorrhea, throat obstruction, edema, jaundice, and malaria. Palmitic acid (PA), oleic acid (OA), ethanol, and acetaminophen liver injuries have been proven to benefit from verbenalin. AIM OF THE STUDY: To study the effects of verbenalin on the prevention of alcoholic steatohepatitis (ASH) through the regulation of oxidative stress and mitochondrial dysfunction by regulating MDMX (Murine double minute X)/PPARα (Peroxisome proliferator-activated receptor alpha)-mediated ferroptosis. MATERIAL AND METHODS: C57BL/6 mice treated with alcohol followed by the Gao-Binge protocol were administered verbenalin by gavage simultaneously. The mitochondrial mass and morphology were visualized using TEM. AML-12 cells were stimulated with ethanol to mimic ASH in vitro. Western blotting, co-immunoprecipitation, and kit determination were simultaneously performed. The target protein of verbenalin was identified by molecular docking, and cellular thermal shift assay (CETSA) further confirmed its interactions. RESULTS: Verbenalin alleviates oxidative stress and ferroptosis in alcohol-associated steatohepatitis. To elucidate the molecular mechanism by which verbenalin inhibits abnormal mitochondrial dysfunction, molecular docking was performed, and MDMX was identified as the target protein of verbenalin. CETSA assays revealed a specific interaction between MDMX and verbenalin. Co-immunoprecipitation demonstrated that PPARα played a critical role in promoting the ability of MDMX to affect ferroptosis. Verbenalin regulates MDMX/PPARα-mediated ferroptosis in AML-12 cells. CONCLUSION: Verbenalin regulates ferroptosis and highlights the therapeutic potential of verbenalin and ferroptosis inhibition in reducing alcoholic steatohepatitis.

A bibliometric and visual analysis of publications on artificial intelligence in colorectal cancer (2002-2022).

Background: Colorectal cancer (CRC) has the third-highest incidence and second-highest mortality rate of all cancers worldwide. Early diagnosis and screening of CRC have been the focus of research in this field. With the continuous development of artificial intelligence (AI) technology, AI has advantages in many aspects of CRC, such as adenoma screening, genetic testing, and prediction of tumor metastasis. Objective: This study uses bibliometrics to analyze research in AI in CRC, summarize the field's history and current status of research, and predict future research directions. Method: We searched the SCIE database for all literature on CRC and AI. The documents span the period 2002-2022. we used bibliometrics to analyze the data of these papers, such as authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analysis were the main methods of analysis. Citespace, VOSviewer, and SCImago Graphica were used to visualize the results. Result: This study selected 1,531 articles on AI in CRC. China has published a maximum number of 580 such articles in this field. The U.S. had the most quality publications, boasting an average citation per article of 46.13. Mori Y and Ding K were the two authors with the highest number of articles. Scientific Reports, Cancers, and Frontiers in Oncology are this field's most widely published journals. Institutions from China occupy the top 9 positions among the most published institutions. We found that research on AI in this field mainly focuses on colonoscopy-assisted diagnosis, imaging histology, and pathology examination. Conclusion: AI in CRC is currently in the development stage with good prospects. AI is currently widely used in colonoscopy, imageomics, and pathology. However, the scope of AI applications is still limited, and there is a lack of inter-institutional collaboration. The pervasiveness of AI technology is the main direction of future housing development in this field.

Multiomics characteristics and immunotherapeutic potential of EZH2 in pan-cancer.

Enhancer of zeste homolog 2 (EZH2) is a significant epigenetic regulator that plays a critical role in the development and progression of cancer. However, the multiomics features and immunological effects of EZH2 in pan-cancer remain unclear. Transcriptome and clinical raw data of pan-cancer samples were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and subsequent data analyses were conducted by using R software (version 4.1.0). Furthermore, numerous bioinformatics analysis databases also reapplied to comprehensively explore and elucidate the oncogenic mechanism and therapeutic potential of EZH2 from pan-cancer insight. Finally, quantitative reverse transcription polymerase chain reaction and immunohistochemical assays were performed to verify the differential expression of EZH2 gene in various cancers at the mRNA and protein levels. EZH2 was widely expressed in multiple normal and tumor tissues, predominantly located in the nucleoplasm. Compared with matched normal tissues, EZH2 was aberrantly expressed in most cancers either at the mRNA or protein level, which might be caused by genetic mutations, DNA methylation, and protein phosphorylation. Additionally, EZH2 expression was correlated with clinical prognosis, and its up-regulation usually indicated poor survival outcomes in cancer patients. Subsequent analysis revealed that EZH2 could promote tumor immune evasion through T-cell dysfunction and T-cell exclusion. Furthermore, expression of EZH2 exhibited a strong correlation with several immunotherapy-associated responses (i.e., immune checkpoint molecules, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) status, and neoantigens), suggesting that EZH2 appeared to be a novel target for evaluating the therapeutic efficacy of immunotherapy.

Cross-Linked Polyphosphazene Nanospheres Boosting Long-Lived Organic Room-Temperature Phosphorescence.

Long-lived organic room-temperature phosphorescence (RTP) has sparked intense explorations, owing to the outstanding optical performance and exceptional applications. Because triplet excitons in organic RTP experience multifarious relaxation processes resulting from their high sensitivity, spin multiplicity, inevitable nonradiative decay, and external quenchers, boosting RTP performance by the modulated triplet-exciton behavior is challenging. Herein, we report that cross-linked polyphosphazene nanospheres can effectively promote long-lived organic RTP. Through molecular engineering, multiple carbonyl groups (C═O), heteroatoms (N and P), and heavy atoms (Cl) are introduced into the polyphosphazene nanospheres, largely strengthening the spin-orbit coupling constant by recalibrating the electronic configurations between singlet (Sn) and triplet (Tn) excitons. In order to further suppress nonradiative decay and avoid quenching under ambient conditions, polyphosphazene nanospheres are encapsulated with poly(vinyl alcohol) matrix, thus synchronously prompting phosphorescence lifetime (173 ms longer), phosphorescence efficiency (∼12-fold higher), afterglow duration time (more than 20 s), and afterglow absolute luminance (∼19-fold higher) as compared with the 2,3,6,7,10,11-hexahydroxytriphenylene precursor. By measuring the emission intensity of the phosphorescence, an effective probe based on the nanospheres is developed for visible, quantitative, and expeditious detection of volatile organic compounds. More significantly, the obtained films show high selectivity and robustness for anisole detection (7.1 × 10-4 mol L-1). This work not only demonstrates a way toward boosting the efficiency of RTP materials but also provides a new avenue to apply RTP materials in feasible detection applications.

lncRNA SNHG26 promoted the growth, metastasis, and cisplatin resistance of tongue squamous cell carcinoma through PGK1/Akt/mTOR signal pathway.

Tongue squamous cell carcinoma (TSCC) is closely linked to head and neck cancers. Here, we sought to explore the role and mechanism of lncRNAs in the occurrence and progression of TSCC and cisplatin resistance. The results of next-generation transcriptomic sequencing revealed that lncRNA-SNHG26 was differentially expressed and was associated with TSCC cisplatin resistance. The Cancer Genome Atlas dataset and tumor tissue analysis revealed that high SHNG26 expression was associated with the occurrence, progression, and poor prognosis of TSCC. Evidence from cell and animal experiments showed that SNHG26 expression was positively correlated with TSCC proliferation, epithelial-mesenchymal transformation, migration, invasion, and cisplatin resistance. Furthermore, in TSCC cells, SNHG26 was found to bind directly to the PGK1 protein, inhibiting its ubiquitination and activating the Akt/mTOR signaling pathway. These findings suggest that lncRNA-SNHG26 may be a promising target for inhibiting TSCC progression and improving sensitivity to cisplatin chemotherapy in TSCC.

Supplemental folic acid and/or multivitamins in pregnancy is associated with a decreased risk of childhood and adolescent nasopharyngeal carcinoma.

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

CYB561A3 is the key lysosomal iron reductase required for Burkitt B-cell growth and survival.

Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma, the leading childhood cancer in sub-Saharan Africa. Burkitt cells retain aspects of germinal center B-cell physiology with MYC-driven B-cell hyperproliferation; however, little is presently known about their iron metabolism. CRISPR/Cas9 analysis highlighted the little-studied ferrireductase CYB561A3 as critical for Burkitt proliferation but not for that of the closely related EBV-transformed lymphoblastoid cells or nearly all other Cancer Dependency Map cell lines. Burkitt CYB561A3 knockout induced profound iron starvation, despite ferritinophagy ad plasma membrane transferrin upregulation. Elevated concentrations of ascorbic acid, a key CYB561 family electron donor, or the labile iron source ferrous citrate rescued Burkitt CYB561A3 deficiency. CYB561A3 knockout caused catastrophic lysosomal and mitochondrial damage and impaired mitochondrial respiration. Conversely, lymphoblastoid B cells with the transforming EBV latency III program were instead dependent on the STEAP3 ferrireductase. These results highlight CYB561A3 as an attractive therapeutic Burkitt lymphoma target.

Glucose oxidase loaded Cu2+ based metal-organic framework for glutathione depletion/reactive oxygen species elevation enhanced chemotherapy.

INTRODUCTION: The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine. METHODS: Here in our study, a Cu2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers. RESULTS: Our results showed that the GOx can catalyze glucose and produce H2O2. In the mean time, the Cu2+ can react with GSH and then transform into Cu+, which resulted in GSH depletion. Afterwards, the produced Cu+ and H2O2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance. DISCUSSION: The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.

Lateral rectus muscle differentiation potential in paralytic esotropia patients.

PURPOSE AND BACKGROUND: Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis. MATERIALS AND METHODS: Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR). RESULTS: A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05). CONCLUSION: The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.

Relationships between IL-1ß, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study.

BACKGROUND: IL-1ß and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1ß, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1ß, TNF-α gene polymorphisms and HBV infection. METHODS: A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1ß, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type. RESULTS: In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1ß rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1ß rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group. CONCLUSION: In the present study, we identified that three polymorphisms (IL-1ß rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

Variant types of Duane retraction syndrome: synergistic divergences and convergences.

PURPOSE: To present the clinical features of 4 patients with Duane retraction syndrome characterized by synergistic divergence or convergence, abnormal vertical movements, and accessory fibrotic bands. METHODS: The medical records of 4 patients were reviewed retrospectively for the following clinical manifestations: visual acuity, refraction, ocular alignments, ocular motility, head position, magnetic resonance imaging, surgical techniques, and outcomes. RESULTS: All 4 cases were diagnosed as variants of Duane retraction syndrome. Two cases (cases 1 and 2) had synergistic divergence with unilateral adduction deficit, and 2 (cases 3 and 4) had synergistic convergence with bilateral abduction deficit. Case 2 manifested abnormal vertical movements of the right eye, which goes down with adduction of the left eye and goes up oppositely with abduction of left eye. Accessory fibrotic bands were detected beside the medial rectus muscle of both eyes in case 3. Synergistic convergence in case 4 occurred only after the first strabismus surgery. Weakening of the misinnervated horizontal rectus muscle improved ocular alignment and head position in cases 1, 3, and 4. CONCLUSIONS: Synergistic divergence and convergence are extremely rare and may present with a great diversity of clinical features. A good outcome is very difficult to achieve; however, weakening of the misinnervated horizontal rectus muscle was therapeutic in these patients.

Etiology and Clinical Features of Diplopia in South China: Analysis of 303 Cases.

PURPOSE: To provide a new classification system for diplopia and evaluate the etiology and clinical features of diplopia subtypes in south China. METHODS: In this retrospective study, all patients presenting with diplopia over the period from 2012 to 2014 in south China were reviewed. Patients were categorized into 3 groups according to their extraocular muscle (EOM) dysfunction: single EOM (sEOM), multiple EOMs (mEOMs), and a comitant strabismus group. Clinical data evaluated included age, sex, medical history, etiology and duration of diplopia, ocular alignment, and ocular motility. RESULTS: A total of 303 patients were enrolled. The most common type of EOM dysfunction was sEOM (158 cases, 52.1%), followed by mEOMs (n = 119, 39.3%), and finally the comitant strabismus group (n = 26, 8.6%). Overall, the most common cause of diplopia involved orbital diseases. Within the sEOM group, microangiopathy (n = 42, 26.6%) and trauma (n = 41, 25.9%) were the major etiologies, with the lateral rectus (LR) (n = 86, 54.4%) being the most frequently involved. There were 12 (4.0%) patients who were considered as nasopharyngeal carcinoma (NPC)-associated diplopia (10 caused by radiation neuropathy following radiation therapy). Thyroid associated ophthalmopathy (TAO, 56 cases, 47.1%) was the predominant etiology found in the mEOMs group. Acute acquired comitant esotropia (AACE, 14 cases, 53.9%) was the most common etiology in the comitant strabismus group. CONCLUSIONS: This new classification system for assessing diplopia as based on EOM dysfunction represents an easy-to-follow approach that can be readily adapted for the clinical use. While microangiopathy and trauma represent common etiologies of diplopia, both orbital diseases and NPC-associated diplopia also warrant special attention when assessing diplopia within patients in south China.

Supramaximal Horizontal Rectus Recession-Resection Surgery for Complete Unilateral Abducens Nerve Palsy.

Purpose: To review the surgical procedures and outcomes of supramaximal horizontal rectus recession-resection surgery for abduction deficiency and esotropia resulting from complete unilateral abducens nerve palsy. Methods: A total of 36 consecutive cases diagnosed as complete abducens nerve palsy, receiving supramaximal medial rectus recession (8.5 ± 1.4 mm, range: 6-10) combined with a supramaximal lateral rectus resection (11.1 ± 1.7 mm, range: 8-14) as performed over the period from 2017 to 2020, were reviewed retrospectively. All surgeries were performed by a single surgeon. Pre- and post-operative ocular motility, ocular alignment, forced duction test, binocular vision, abnormal head posture, and surgical complications were assessed. Results: Of these 36 cases, 23 (63.8%) were followed up for greater than 2 months (Mean ± SD = 8.4 ± 6.0, range: 2-24) after surgery and the collected data was presented. Mean ± SD age of these patients was 41.7 ± 14.4 (range: 12-67) years with 73.9% being female. Trauma (52.2%, 12/23) and cerebral lesions (21.7%, 5/23) were the primary etiologies for this condition. Esodeviation in primary position improved from 55.5 ± 27.2 prism diopters (PD) (range: +25 to +123) to 0.04 ± 7.3 PD (range: -18 to +12) as assessed on their last visit. Pre-operative abduction deficits of -5.6 ± 1.0 (range: -8 to -4) reduced to -2.4 ± 1.4 (range: -4 to 0) post-operatively. The mean dose-effect coefficient of 2.80 ± 1.20 PD/mm (range: 1.07-6.05) was positively correlated with pre-operative esodeviation. Rates of overcorrection and ortho were 69.6 and 26.1%, respectively, on the first day after surgery, while on their last visit the respective levels were 4.3 and 82.6%. Conclusion: Supramaximal horizontal rectus recession-resection surgery is an effective treatment method for complete abduction deficiency. The dose-effect was positively correlated with pre-operative esodeviation. Overcorrection on the first day post-operatively is required for a long-term satisfactory surgical outcome.