Probabilistic human health risk assessment of PCDD/Fs near municipal solid-waste incinerator using Monte Carlo analysis coupled with triangular fuzzy numbers.

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.

Vacuum Based Gas Sensing Material Characterization System for Precise and Simultaneous Measurement of Optical and Electrical Responses.

Gas sensing performance characterization systems are essential for the research and development of gas sensing materials and devices. Although existing systems are almost completely automatically operated, the accuracies of gas concentration control and of pressure control and the ability to simultaneously detect different sensor signals still require improvement. In this study, a high-precision gas sensing material characterization system is developed based on vacuum technology, with the objective of enabling the precise and simultaneous measurement of electrical responses. Because of the implementation of vacuum technology, the gas concentration control accuracy is improved more than 1600 times, whereas the pressure of the test ambient condition can be precisely adjusted between vacuum and 1.2 bar. The vacuum-assisted gas-exchanging mechanism also enables the sensor response time to be determined more accurately. The system is capable of performing sensitivity, selectivity, and stability tests and can control the ambient relative humidity in a precise manner. More importantly, the levels of performance of three different optical signal measurement set-ups were investigated and compared in terms of detection range, linearity, noise, and response time, based on which of their scopes of application were proposed. Finally, single-period and cyclical tests were performed to examine the ability of the system to detect optical and electrical responses simultaneously, both at a single wavelength and in a spectral region.

Progress on genomics and locus of important agronomic traits in Chenopodium quinoa.

Quinoa (Chenopodium quinoa, Willd.) as a new health food in the 20th century, its comprehensive nutritional composition, stress resistance and other characteristics have been paid much of attention, and enjoys the reputation of "nutritional gold", "vegetarian king" and "food in the future" in the world. In recent years, with the rapid development of genomics and high-throughput sequencing technology, the high-quality whole genome sequence of quinoa has been completed, and the omics analysis and functional research of a series of key genes have been gradually carried out. In this review, we summarize the research progress in quinoa genomics, gene family analysis of important transcription factors, genetic map construction, QTL mapping of important traits, and genes for important agronomic and yield traits. Moreover, according to the current status of quinoa breeding, this paper also put forward five key problems in quinoa breeding, and pointed out four important directions of genetic improvement and breeding of quinoa in the future, so as to provide reference for the realization of directional genetic improvement of quinoa in the future.

Development of Drought-Tolerant Transgenic Wheat: Achievements and Limitations.

Crop yield improvement is necessary to keep pace with increasing demand for food. Due to climatic variability, the incidence of drought stress at crop growth stages is becoming a major hindering factor to yield improvement. New techniques are required to increase drought tolerance along with improved yield. Genetic modification for increasing drought tolerance is highly desirable, and genetic engineering for drought tolerance requires the expression of certain stress-related genes. Genes have been identified which confer drought tolerance and improve plant growth and survival in transgenic wheat. However, less research has been conducted for the development of transgenic wheat as compared to rice, maize, and other staple food. Furthermore, enhanced tolerance to drought without any yield penalty is a major task of genetic engineering. In this review, we have focused on the progress in the development of transgenic wheat cultivars for improving drought tolerance and discussed the physiological mechanisms and testing of their tolerance in response to inserted genes under control or field conditions.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway.

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy.

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.

Delayed surgical management is not effective for severe Bell's palsy after two months of onset.

AIMS: To assess the effectiveness of delayed surgery and follow-up observation in managing severe Bell's palsy after two months of onset. METHODS: Forty-one Bell's palsy patients with severe facial paralysis were treated after two months of onset. Eighteen patients in group I underwent decompression operations between two and three months after onset, and eight patients in group II underwent surgery after three months of onset; 15 patients in group III were managed with follow-up observation. All patients were followed up at the end of 3rd, 6th and 12th months, and surgical outcomes were compared with follow-up observations using House-Brackmann score and Facial Clinimetric Evaluation (FaCE) scale. RESULTS: Between groups I and III, the difference in the proportion of the patients with fair or poor recoveries was statistically significant (p < 0.05) at the three-month follow-up visit. There was no significant difference in the distribution of complete, fair or poor recoveries at the 12-month follow-up visits among the three groups (p < 0.05). The total FaCE score and five individual domains were significantly improved at the end of the follow-up period in groups I and III (p < 0.05). However, in group I, the lacrimal control scores were significantly decreased at the end of the follow-up period compared to scores before surgery (p < 0.05). After surgery, four patients had sensorineural hearing loss, three patients had tinnitus and no patients had vertigo. CONCLUSION: Patients with severe Bell's palsy after two months of onset would not benefit from delayed decompression surgery.

Identification and health risk evaluation of soil contaminated by polycyclic aromatic hydrocarbons at shale gas extraction sites based on positive matrix factorization.

The impact of shale gas extraction on surrounding environmental media remains unclear. In this study, the current state of contamination by polycyclic aromatic hydrocarbons (PAHs), which are high-frequency contaminants of shale gas, was investigated in the soil surrounding emerging shale gas development sites. The source analysis of PAHs was conducted in the soils of shale gas extraction sites using positive matrix factorization (PMF). The health risk assessment (HRA) was calculated for ingestion, dermal contact, and inhalation exposures, and the priority sources of PAHs in the soil were jointly identified by PMF and HRA to refine the contribution level of different individual PAHs to the carcinogenic risk. The results showed that both Sichuan and Chongqing mining site soils were contaminated to different degrees. Shale gas extraction has an impact on the surrounding soil, and the highest contributing source of PAHs in the mining site soil of Sichuan was anthropogenic activity, accounting for 31.6%, whereas that in the mining site soil of Chongqing was biomass combustion and mixed automobile combustion, accounting for 35.9%. At the two mining sites in Sichuan and Chongqing, none of the three exposure pathways (ingestion, dermal contact, and inhalation) posed a carcinogenic risk to children, whereas the dermal exposure pathway posed a carcinogenic risk to adults. Health risk assessments based on specific source assignments indicate that when managing soil pollution, the control of fossil fuel combustion and vehicular emissions should be prioritized.

Salvinorin A ameliorates pilocarpine-induced seizures by regulating hippocampal microglia polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum (Epling and Játiva) is a psychoactive plant traditionally used by the Latinos for various medicinal purposes. Salvinorin A (Sal A), the main bioactive constituent of S. divinorum, is a natural highly selective kappa opioid receptor (KOR) agonist. Considering the anti-inflammatory effect of S. divinorum and endogenous hippocampal dynorphin/kappa opioid receptor (KOR) system playing an anticonvulsant function, we hypothesis that Sal A can be a potential candidate to treat epilepsy. Here, we identified whether Sal A ameliorated epileptic seizures and neuronal damages in animal model and in vitro model and investigated its underlying mechanisms. MATERIALS AND METHODS: Mice epilepsy model was induced by pilocarpine following seizures assessed by Racine classification. Hippocampus tissues were obtained for genetic, protein, and histological investigation. Furthermore, lipopolysaccharide (LPS)-activated BV2 microglial cells were utilized to validate the anti-inflammatory and microglia polarization regulation effects of Sal A. RESULTS: Sal A treatment significantly prolonged the latency to status epileptics (SE) and shortened the duration of SE in the pilocarpine-induced model. It also alleviated neuronal damages via activation of the AMPK/JNK/p-38 MAPK pathway and inhibition of apoptosis-related protein in hippocampus tissues. Furthermore, Sal A dose-dependently reduced microglia-mediated expression of pro-inflammatory cytokines and increased anti-inflammatory factors levels in SE mice and LPS-activated BV2 microglial cells by regulating microglia polarization. In addition, the effect of Sal A in vitro was totally blocked by KOR antagonist nor-BNI. CONCLUSION: Sal A treatment protects against epileptic seizures and neuronal damages in pilocarpine-induced models by suppressing the inflammation response through regulating microglial M1/M2 polarization. This study might serve as a theoretical basis for clinical applications of Sal A and its analogs and provide a new insight into the development of anti-seizure drugs.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

Effects of spraying cycocel and delaying nitrogen application on lodging resistance and yield formation of winter wheat.

We conducted a 3-year (2017-2020) field experiment in the wheat base of Jinzhong Agricultural Hi-tech Industries Demonstration Zone, aiming to determine the measures of nitrogen topdressing and the regulatory effect of cycocel in spring to increase wheat yield. Four nitrogen topdressing dates were set up under the condition of cycocel spraying and control (CK) during the rising period: 10 days (D10), 20 days (D20), 30 days (D30), and 40 days (D40) after regreening stage, to analyze the impact of different N topdressing dates on winter wheat yield and the regulation effect of cycocel on stem characteristics, lignin content and related synthetase activities. The results showed that compared to other nitrogen topdressing dates, D30 increased spike number by 1.4%-5.2%, grain number per spike by 0.4%-12.0%, 1000-grain weight by 1.7%-9.4% and yield 8.8%-22.1% respectively. Compared to D10 and D20, D30 significantly improved the activities of phenylalanine ammonia-lyase (PAL) at 0-21 days and 35-42 days after the formation of the second section and increased that of tyrosine ammonia-lyase (TAL) at 0-42 days after the formation of the second section, and increased the lignin content of stem, the internode quality, and the breaking resistance of stem, reduced plant height, and thereby improved the lodging resistance. However, D40 increased grain number per spike by 4.5%-10.1% and yield 0.04%-11.3%, but reduced the activities of PAL and TAL at 0-42 days after the formation of the second internode, reduced the lignin content, weakened the stem strength, and increased the risk of lodging. After spraying cycocel, plant height decreased significantly, the activities of PAL and TAL enhanced, the lignin content in internodes increased, the stem strength advanced, and reached a significant level under D30. Under the condition of nitrogen topdressing combined with cycocel spraying in spring, PAL and TAL activities were significantly positively correlated with lignin content. Lignin content was significantly positively correlated with stem breaking resistance. Stem breaking resistance was significantly positively correlated with lodging resistance index. Yield and its components were significantly posi-tively correlated with internode diameter, weight and breaking resistance, and significantly negatively correlated with plant height and internode length. Overall, nitrogen topdressing combined with spraying cycocel 30 days after regreening could promote the synthesis and accumulation of lignin, and improve stem plumpness, plant lodging resistance and yield.

Effects of sowing patterns on nitrogen utilization and yield formation of winter wheat in the western Huang-Huai-Hai region.

To examine the differences of three improved sowing methods in winter wheat yield and nitrogen efficiency and reveal the characteristics responsible for such differences, we conducted field experiments in the Jinnan area of the western Huang-Huai-Hai wheat region for three consecutive seasons from 2016 to 2019. The three improved sowing methods were wide space sowing (WSS), furrow sowing in moisture soil (FS), and three-dimensional uniform sowing (TDUS), with conventional drilling sowing (CDS) as the control. The results showed that meteorological factors such as accumulated temperature, solar radiation, and precipitation in the growing seasons from 2016 to 2019 showed great intra- and inter-annual variations. Compared with CDS, the improved sowing methods (WSS, FS, and TDUS) enhanced spike number per unit area and increased grain yield in three growing seasons by 18.3%-55.5%, 8.6%-22.2%, and 10.9%-39.5%, respectively. The three methods increased nitrogen uptake efficiency (NEup) by 5.8%-57.1%, pre-flowering nitrogen transfer ratio (Np/Nt) by 3.0%-15.3%, and nitrogen efficiency by 7.9%-35.7%, respectively. We developed a structural equation model (SEM) by integrating meteorological factors and experimental variables. The results showed that the three improved sowing methods could reduce the effects of extreme low temperature on wheat plant population, increase NEup and Np/Nt, and provide sufficient nitrogen supply to the grains of high-spike number wheat population for high yield and high nitrogen efficiency. In summary, our results demonstrated that WSS, FS, and TDUS all improved NEup and Np/Nt in the 2016-2017 season when meteorological conditions were favorable for wheat growth, and enhanced yield components with high SN, leading to high yield and high nitrogen efficiency. In contrast, in both 2017-2018 and 2018-2019 seasons with extremely low temperature and uneven distribution of meteorological conditions, WSS had a higher number of tillers at the jointing stage and enhanced pre-flowering nitrogen uptake and translocation, whereas TDUS had a relatively stable nitrogen uptake rate, leading to a stable grain yield.

[Effects of Long-term Tillage on Soil Bacterial Community Structure and Physicochemical Properties of Dryland Wheat Fields in Northern China].

To explore the effects of long-term tillage on bacterial community structure in different soil layers of dryland wheat fields and its relationship with soil physicochemical properties, a long-term field experiment was conducted from 2016 to 2021 in Wenxi Experimental Demonstration Base of Shanxi Agricultural University, Shanxi Province. We studied the effects of no-tillage (NT), subsoiling-tillage (ST), and deep plowing (DP) on soil physicochemical properties; α and ß diversity of the bacterial community; and dominant and different species of phyla and genera in different soil layers. Additionally, PICRUSt2 was used to predict the metabolic function of soil bacterial community. The results revealed that subsoiling-tillage and deep plowing significantly increased the soil water content in the 20-40 cm soil layer and significantly decreased the soil organic carbon content in the 0-20 cm soil layer compared with that under no-tillage for five consecutive years. Compared with that under deep plowing, subsoiling-tillage significantly increased soil water content, soil organic carbon content, dissolved organic carbon content, and dissolved organic nitrogen content in the 0-20 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing increased the α diversity of the soil bacterial community in the 0-40 cm soil layer, and subsoiling-tillage was higher than deep plowing. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundances of Acidobacteria and Nitrospirae in the 0-20 cm soil layer and Acidobacteria, Chloroflexi, Gemmatimonadetes, Rokubacteria, GAL15, and Nitrospirae in the 20-40 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundance of Nitrospira in the 0-20 cm soil layer and Rubrobacter and Streptomyces in the 20-40 cm soil layer. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundance of Acidobacteria and Gemmatimonadetes in the 0-40 cm soil layer. Redundancy analysis demonstrated that the contents of soil organic carbon, dissolved organic carbon, and dissolved organic nitrogen in the 0-20 cm soil layer exerted positive effects on Actinobacteria and Blastococcus, and the soil water content in the 0-40 cm soil layer exerted positive effects on Acidobacteria, Chloroflexi, and Gemmatimonadetes under subsoiling-tillage. The results of PICRUSt2 prediction showed that subsoiling-tillage and deep plowing significantly increased the relative abundance of amino acid metabolism and the metabolism of cofactors and vitamins but decreased the relative abundance of lipid metabolism of bacterial communities in the 20-40 cm soil layer compared with that under no-tillage. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundances of amino acid metabolism in the 0-40 cm soil layer and other amino acid metabolism in the 0-20 cm soil layer. In conclusion, subsoiling-tillage or deep plowing could increase the soil water content, α diversity of the soil bacterial community, and their metabolic capacity in the dryland wheat fields during the summer fallow period. The relative abundance of Acidobacteria and Gemmatimonadetes and the ability of amino acid metabolism of the bacterial community were increased by subsoiling-tillage, and thus the contents of soil dissolved organic carbon and dissolved nitrogen can be increased.

CCNB1 is a novel prognostic biomarker and promotes proliferation, migration and invasion in Wilms tumor.

BACKGROUND: Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies. METHODS: High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments. RESULTS: We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with 'cell cycle', 'DNA replication'. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients' overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays. CONCLUSION: Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.

Nomogram for predicting non-proliferative vitreoretinopathy probability after vitrectomy in eyes with rhegmatogenous retinal detachment.

AIM: To identify the risk factors for postoperative proliferative vitreoretinopathy (PVR) in patients with primary rhegmatogenous retinal detachment (RRD) and develop a nomogram for predicting postoperative PVR-free probability. METHODS: A total of 741 patients (741 eyes) diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set. Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-, 4-, 5-, and 6-month postoperative PVR-free probabilities. Nomogram performance was estimated by the concordance index (C-index), calibration plot, and the area receiver operating characteristic (ROC) curve. RESULTS: A nomogram was constructed based on the preoperative PVR, silicone oil tamponade time (SOTT), photocoagulation energy (PE), retinal tear size (RTS), and hypertension. In the training set, the C-index of the nomogram was 0.896, 0.936, 0.961, and 0.972 at 3, 4, 5, and 6mo, respectively. The C-index values in the validation set were 0.860, 0.936, 0.951, and 0.965 at 3, 4, 5, and 6mo, respectively. Decision-curve analysis indicated that only the 4-, 5-, and 6-month nomograms had significant net benefits over a large threshold probabilities interval. CONCLUSION: Preoperative PVR, SOTT, PE, RTS, and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD. The proposed nomogram can effectively predict the 4-, 5-, and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

A novel method for three-dimensional analysis of endoscopic spatial relationships of pterygopalatine fossa structures and associated regions.

BACKGROUND: The spatial orientation rules of the important skull base structures are essential for performing endoscopic surgery. However, there is no satisfactory three-dimensional (3-D) anatomy study available to the surgeon at present. The aims of this study are to construct a new method to learn the spatial orientation of anatomical features under endoscopy and to help the surgeon establish a 3-D image of skull base structures in his mind. METHODS: A modified MicronTracker navigation system was used to measure the pitch angle, direction angle and distance from the reference points to various anatomical landmarks of the pterygopalatine fossa and related structures (PPFRS) at the skull base in 10 fresh cadavers (20 sides). RESULTS: The location data of the positions of the major landmarks were acquired and a digital model of the anatomical structures of the PPFRS was built, which can be moved, whirled or demonstrated easily. CONCLUSION: It is practical to measure the positions of the anatomical structures of the PPFRS with a modified binocular vision-based MicronTracker navigation system. It is a valuable exploration tool to help the surgeon establish the orientation of surgical landmarks in his mind by the 3-D parameters and model.

[Diagnosis and treatment of diverticulums in laryngopharynx and cervical esophagus].

OBJECTIVE: To explore the clinical presentations, diagnosis and treatment of diverticulums in laryngopharynx and cervical esophagus. METHODS: Nineteen cases of diverticulums in laryngopharynx and cervical esophagus with general clinical information available from 1985 to 2010 at Peking Union Medical College Hospital were reviewed retrospectively and analyzed with a literature review. RESULTS: One case of lateral hypopharyngeal pouch presented with fetor oris and pharyngalgia. Three cases of Killian-Jamieson diverticulums had fetor oris and dysphagia. Among 15 cases of Zenker diverticulums, 3 had fetor oris, sour regurgitation and dysphagia while another 12 cases were asymptomatic. Seven patients with subjective complaints underwent diverticulectomy through open surgeries or endoluminal approaches and their symptoms were resolved and no recurrences were found during a follow-up period of 6 months-18 years. In 12 cases of asymptomatic Zenker diverticulums, observation was adopted and there was no complaint during a follow-up period of 1 - 25 years. CONCLUSION: Lateral hypopharyngeal pouch, Killian-Jamieson diverticulum and Zenker's diverticulum are rare entities with different clinical presentations. For symptomatic diverticulum, the most common treatment is surgical resection of diverticulectom and the prognosis is satisfactory. But for asymptomatic diverticulum, observation suffices.

KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

Dynorphin promotes stress-induced depressive behaviors by inhibiting ventral pallidal neurons in rats.

AIM: Endogenous dynorphin signaling via kappa opioid receptors (KORs) plays a key role in producing the depressive and aversive consequences of stress. We investigated the behavioral effects of the dynorphin/KOR system in the ventral pallidum (VP) and studied the underlying mechanisms. METHODS: To investigate the effects of dynorphin on the VP, we conducted behavioral experiments after microinjection of drugs or shRNA and brain-slice electrophysiological recordings. Histological tracing and molecular biological experiments were used to identify the distribution of KORs and the possible sources of dynorphin projections to the VP. RESULTS: An elevated dynorphin concentration and increased KOR activity were observed in the VP after acute stress. Infusion of dynorphin-A into the VP produced depressive-like phenotypes including anhedonia and despair and anxiety behaviors, but did not alter locomotor behavior. Mechanistically, dynorphin had an inhibitory effect on VP neurons-reducing their firing rate and inhibiting excitatory transmission-through direct activation of KORs and modulation of downstream G-protein-gated inwardly rectifying potassium (GIRK) channels and high-voltage gated calcium channels (VGCCs). Tracing revealed direct innervation of VP neurons by dynorphin-positive projections; potential sources of these dynorphinergic projections include the nucleus accumbens, amygdala, and hypothalamus. Blockade of dynorphin/KOR signaling in the VP by drugs or viral knock-down of KORs significantly reduced despair behavior in rats. CONCLUSIONS: Endogenous dynorphinergic modulation of the VP plays a critical role in mediating depressive reactions to stress.

Outcomes of a novel bubble ultra-wide field viewing system for vitreoretinal surgery.

PURPOSE: To report the clinical outcomes and evaluate the efficacy of a novel bubble ultra-wide field viewing system for vitreoretinal surgery. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred and fifty-one eyes of 146 consecutive patients with proliferative diabetic retinopathy (PDR), vitreous haemorrhage originating from retinal vein occlusion (VH-RVO), epiretinal membrane (EM), macular hole (MH) or retinal detachment (RD) who underwent vitreoretinal surgery using the bubble ultra-wide field viewing system were included. METHODS: A standard phacoemulsification was performed on each patient. Core humour and mid-peripheral vitreous humour were removed using a planoconcave lens. A suitably sized bubble was infused to attach to the posterior capsule or the anterior chamber depending on the integrity of the posterior capsule. The planoconcave lens and the air bubble formed the wide-angle viewing system, through which peripheral vitrectomy was performed. MAIN OUTCOME MEASURES: Range of applications, field of view, model validation and complications were recorded. RESULTS: The new ultra-wide field viewing system was successfully applied in all eyes, including 34 with PDR, 28 VH-RVO, 28 EM, 25 MH and 36 RD. Peripheral vitrectomy, local or panretinal laser photocoagulation, and removal of the peripheral proliferative membrane were successfully performed while viewing through this system. Maximum peripheral retinal area observable during the procedure was positively correlated with pupil diameter. Model analysis results showed that when the pupil diameter was 6 mm, the maximum field of view was approximately 128.1- 148.0 degrees with this system. Of 142 eyes, the main intraoperative complication was iatrogenic retinal breaks (IRBs) in 8 eyes (5.3%) and posterior capsule injury by vitreous cutter during bubble removal in 6 eyes (4.2%). The postsurgery mean best-corrected visual acuity (BCVA) (0.48 ± 0.39 logMAR) was significantly improved compared with the preoperative mean BCVA (1.60 ± 1.08 logMAR, p < 0.001). No incidents of postoperative choroidal detachment, secondary glaucoma or endophthalmitis were recorded. CONCLUSIONS: For patients with lens excision or absence, vitreoretinal surgery can be successfully performed using the novel viewing system described here. The system is a safe, convenient and economical ultra-wide field viewing system with a wide range of applications.