Depression and dental caries in US adults, NHANES 2015-2018.

PURPOSE: This study aimed to investigate the link between depression and untreated dental caries among adults in the United States. METHODS: Data were collected from the National Health and Nutrition Survey (2015-2018); respondents aged 20 years or older who completed a patient health questionnaire and underwent a comprehensive oral examination were included. Participants were categorized into three groups according to depressive symptoms as follows: those with no, mild, or moderate to severe depression. Data were weighted, and multiple potential covariates were included in the analysis to provide national estimates and account for the complex sample design. A multivariable weighted logistic regression model was performed to test the hypothesis that varying degrees of depression in American adults are associated with untreated dental caries. Subgroup analyses were performed based on age and gender after adjusting for potential covariates. A P value of <.05 was considered significant. RESULTS: Among 8740 participants, the prevalence of untreated coronal and root caries was 20.50% and 12.92%, respectively. Moderate to severe depression was a significant risk factor (odds ratio, 1.25; 95% confidence interval, 1.09-1.66) for untreated root caries. The risk of untreated root caries increased by 87% in young adults (aged 20-44 years) and by 46% in women with moderate to severe depression. The suest analysis revealed that the impact of moderate to severe depressive disorder on untreated root caries was non-significantly different between the age subgroup (p=0.09) and sex subgroup (p=0.51). However, depression was non-significantly associated with untreated coronal caries (mild depression: OR, 1.07; 95% CI, 0.85-1.34; moderate to severe depression 1.06; 95% CI, 0.83-1.36; respectively). CONCLUSION: The results of this study suggested a significant association between moderate and severe depression and untreated root caries; however, the association with untreated coronal caries was non-significant. In the United States, moderate and severe depression in adults is associated with root caries.

Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a prevalent and aggressive malignancy in the digestive tract, requiring accurate prediction and effective treatment strategies. Recently, the discovery of disulfidptosis, a novel form of programmed cell death characterized by abnormal disulfide accumulation, has sparked interest in its role in PAAD. In this study, we aimed to investigate the involvement of disulfidptosis-related genes (DRGs) in PAAD. Using publicly available databases, we conducted a comprehensive analysis exploring the complex relationships between DRGs and important aspects of PAAD, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we observed significant heterogeneity among different disulfidptosis subclusters and identified specific differentially expressed genes in PAAD. Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration. This study presents exciting opportunities and challenges in unraveling the underlying mechanisms of PAAD prognosis. It also establishes a foundation for personalized cancer care and the development of innovative immunotherapeutic strategies. By shedding light on the role of DRGs, particularly hub genes, we enhance our understanding and management of PAAD.

Optimising oral cancer reconstruction: a retrospective cohort study on the modified radial forearm free flap technique to eliminate the need for a secondary donor site.

The radial forearm free flap (RFFF) is commonly used in the reconstruction of oral cancer patients. Traditional RFFF (TRFFF) techniques, which often require a secondary donor site to repair the forearm defect, may result in a scar extending to the dorsal hand. This can lead to significant functional and aesthetic concerns in the forearm. We designed a modified RFFF (MRFFF) that incorporates a glasses-shaped flap and features deep venous drainage. To evaluate its effectiveness we conducted a retrospective chart review of 105 patients with oral squamous cell carcinoma who underwent reconstructive surgery between 2018 and 2022. These patients were treated either with a TRFFF (n = 60) or the newly developed MRFFF (n = 45). Our inclusion criteria, guided by preliminary surgical experience prior to initiating the study, stipulated that single oral defects should be no larger than 6 × 6 cm2, and adjacent double defects no larger than 3 × 6 cm2. Flap size, pedicle length, harvesting duration, and anastomosis during the surgical procedure were compared between the two techniques. Preoperative and postoperative oral function, recurrence, mortality, and dorsal scarring were recorded. One-week, one-month, and six-month postoperative subjective aesthetics assessments, and self-reported postoperative donor hand function, were measured using the Michigan hand questionnaire (MHQ). There were no significant differences between the groups in terms of flap size, pedicle length, harvesting time, anastomosis time, postoperative oral function, recurrence, and mortality. However, patients with a MRFFF did not require a second donor graft site and did not have scars extending to the dorsal forearm. They also had significantly improved postoperative aesthetic outcomes (1 week: 70.6%, 1 month: 62.2%) and donor hand function (1 week: 54.6%, 1 month: 40.4%) compared with the TRFFF group (p < 0.001). The MRFFF eliminates the need for secondary donor sites and improves primary donor site outcomes. It is versatile and can be employed for either single or composite oral defects. Through extensive case studies, we have defined its specific scope: it is suitable for single defects measuring no more than 6 × 6 cm2, or for composite defects no larger than 3 × 6 cm2. Furthermore, it does not compromise the functional recovery of the recipient site, and should be widely adopted for all qualifying patients.

Adjuvant Therapy-Free Strategy for Stage IB to IIIA Non-Small-Cell Lung Cancer Patients After Radical Resection Based on Longitudinal Undetectable Molecular Residual Disease: Prospective, Multicenter, Single-Arm Study (CTONG 2201).

BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy. PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled. CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).

Craniomaxillofacial Bone Segmentation and Landmark Detection Using Semantic Segmentation Networks and an Unbiased Heatmap.

Craniomaxillofacial (CMF) surgery always relies on accurate preoperative planning to assist surgeons, and automatically generating bone structures and digitizing landmarks for CMF preoperative planning is crucial. Since the soft and hard tissues of the CMF regions possess complicated attachment, segmenting the CMF bones and detecting the CMF landmarks are challenging problems. In this study, we proposed a semantic segmentation network to segment the maxilla, mandible, zygoma, zygomatic arch, and frontal bones. Then, we obtained the minimum bounding box around the CMF bones. After cropping, we used the top-down heatmap landmark detection network, similar to the segmentation module, to identify 18 CMF landmarks from the cropping patch. In addition, an unbiased heatmap encoding method was proposed to generate actual landmark coordinates in the heatmap. To overcome quantization effects in the heatmap-based landmark detection networks, the distribution-prior coordinate representation of medical landmarks (DCRML) was proposed to utilize the prior distribution of the encoding heatmap, approximating the accurate landmark coordinates in heatmap decoding by Taylor's theorem. The encoding and decoding method can easily contribute to other existing landmark detection frameworks based on heatmaps; consequently, these approaches can readily benefit without changing model structure. We used prior segmentation knowledge to enhance the semantic information around the landmarks, increasing landmark detection accuracy. The proposed framework was evaluated by 100 healthy persons and 86 patients from multicenter cooperation. The mean Dice score of our proposed segmentation network achieved over 88 %; in particular, the mandible accuracy was approximately 95%. The mean error of landmarks was 1.84 ±1.32 mm.

Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma.

Lower-grade glioma (LGG), a prevalent malignant tumor in the central nervous system, requires accurate prediction and treatment to prevent aggressive progression. We aimed to explore the role of disulfidptosis-related genes (DRGs) in LGG, a recently discovered form of programmed cell death characterized by abnormal disulfide accumulation. Leveraging public databases, we analyzed 532 LGG tumor tissues (The Cancer Genome Atlas), 1,157 normal samples (Genotype-Tissue Expression), and 21 LGG tumor samples with 8 paired normal samples (GSE16011). Our research uncovered intricate relationships between DRGs and crucial aspects of LGG, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we identified significant heterogeneity among disulfidptosis sub-clusters and elucidated specific differential gene expression in LGG, with myeloid cell leukemia-1 (MCL1) as a key candidate. Machine learning techniques validated the relevance of MCL1, considering its expression patterns, prognostic value, diagnostic potential, and impact on immune infiltration. Our study offers opportunities and challenges to unravel potential mechanisms underlying LGG prognosis, paving the way for personalized cancer care and innovative immunotherapeutic strategies. By shedding light on DRGs, particularly MCL1, we enhance understanding and management of LGG.

Identification of disulfidptosis-related genes with immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant primary tumor that is usually diagnosed at an advanced stage; thus, there is an urgent need for efficient and sensitive novel diagnostic markers to determine the prognosis and halt disease progression in patients with HCC. Disulfidptosis is a recently discovered form of programmed cell death, essentially an abnormal accumulation of intracellular bisulfides. Therefore, our study aimed to investigate the role of disulfidptosis-related genes (DRGs) in the pathogenesis of HCC. Based on public databases, our work demonstrates the relationship between DRG and expression, immunity, mutation/drug sensitivity, and functional enrichment in HCC. We also revealed the significant heterogeneity of HCC in different DRGs sub-clusters and in differentially expressed genes (DEGs), respectively. Subsequently, the most relevant candidate gene, SLC7A11, was screened by machine learning to further validate the significance of SLC7A11 in the clinical features, prognosis, nomogram pattern, and immune infiltration of HCC. Our study, which elucidates the potential mechanisms of DRGs and HCC, reveals that SLC7A11 can serve as a novel prognostic biomarker and provides opportunities and challenges for individualized cancer immunotherapy strategies.

Early and Persistent Dysphagia Relief Predicts Tumor Response in Esophageal Squamous Cell Carcinoma Patients Treated with Immunochemotherapy.

BACKGROUND: In this prospective study, we aimed to investigate the role of patient-reported dysphagia relief in predicting pathological tumor responses to neoadjuvant immunochemotherapy (NAIC) in locally advanced esophageal squamous cell carcinoma (ESCC) patients. METHODS: This study was designed as a multi-center, prospective study including ESCC patients who received NAIC in the discovery and validation cohorts. The patients' responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES 18 and QLQ-C30 were collected at multiple time points. Subsequent time point-intensive esophageal cancer-specific dysphagia trajectories were depicted using growth mixture modeling (GMM) analysis. Furthermore, univariate and multivariate binary logistic regression was used to assess the independent predictors for pathological tumor responses. RESULTS: A total of 120 patients from the discovery cohort and 42 patients from the validation cohort were included in the analysis. In the discovery cohort, 19 (22.9%) of the 83 patients achieved pCR status. In the independent validation cohort, 24 patients underwent surgery, and 9 (37.5%) patients achieved pCR status. Trajectory analysis showed that, in the pCR group, the beginning of rapid declines in the slope occurred on days 3, 6, and 9. Further multivariate analysis showed that the degree of dysphagia relief (△dysphagia%) was the only significant independent predictor for pCR status (OR = 3.267, 95% CI 1.66-6.428, P < 0.001). The AUC value for △dysphagia% was 0.961 (95% CI: 0.922-0.999, P < 0.001). CONCLUSION: The current study demonstrated that a longitudinal patient-reported outcome (PRO) was an easily obtained, cost-effective, and noninvasive tool for predicting tumor responses to neoadjuvant immunochemotherapy.

The XylR/NtrC-type regulator CbsR positively regulates upstream pathway of chlorobenzene degradation in Pandoraea pnomenusa.

AIMS: Pandoraea pnomenusa MCB032 completely degrades chlorobenzene, whose metabolic pathway is encoded by cbs and clc gene clusters. The putative regulatory factors ClcR and CbsR are predicted to regulate the cbs and clc gene clusters. This research aims to understand the function of ClcR and CbsR. METHODS AND RESULTS: RT-PCR analyses demonstrated that the cbsFAaAbAcAdB operon that encodes catabolic pathways for the degradation of chlorobenzene to chlorocatechol is located on an operon. Moreover, the clcABCDE operon is involved in the 3-chlorocatechol pathway. Gene knockout and transcriptional analysis showed that the transcription of the cbsFAaAbAcAdB operon is positively regulated by CbsR, whereas the clcABCDE operon is activated by ClcR. Primer extension analysis was used to locate the transcription start sites of the cbsFAaAbAcAdB and cbsR operons. Electrophoretic mobility shift assay analyses showed that CbsR is bound to the sites in the promoter regions of cbsFAaAbAcAdB and cbsR operons. CONCLUSION: The XylR/NtrC-type regulator CbsR positively regulates the transcription of the cbsFAaAbAcAdB operon encoding the upstream pathway of chlorobenzene catabolism, while the LysR-type regulator ClcR activates the clcABCDE operon encoding the downstream pathway.

Microbial detoxification of 3,5-xylenol via a novel process with sequential methyl oxidation by Rhodococcus sp. CHJ602.

The compound 3,5-xylenol is an essential precursor used in pesticides and industrial intermediate in the disinfectants and preservatives industry. Its widespread application makes it an important source of pollution. Microbial bioremediation is more environmentally friendly than the physicochemical treatment process for removing alkylphenols from a polluted environment. However, the 3,5-xylenol-degrading bacteria is unavailable, and its degradation mechanism remains unclear. Here, a 3,5-xylenol-metabolizing bacterial strain, designated Rhodococcus sp. CHJ602, was isolated using 3,5-xylenol as the sole source of carbon and energy from a wastewater treatment factory. Results showed that strain CHJ602 maintained a high 3,5-xylenol-degrading performance under the conditions of 30.15 °C and pH 7.37. The pathway involved in 3,5-xylenol degradation by strain CHJ602 must be induced by 3,5-xylenol. Based on the identification of intermediate metabolites and enzyme activities, this bacterium could oxidize 3,5-xylenol by a novel metabolic pathway. One methyl oxidation converted 3,5-xylenol to 3-hydroxymethyl-5-methylphenol, 3-hydroxy-5-methyl benzaldehyde, and 3-hydroxy-5-methylbenzoate. After that, another methyl oxidation is converted to 5-hydroxyisophthalicate, which is metabolized by the protocatechuate pathway. It is catalyzed by a series of enzymes in strain CHJ602. In addition, toxicity bioassay result indicates that 3,5-xylenol is toxic to zebrafish and Rhodococcus sp. CHJ602 could eliminate 3,5-xylenol in water to protect zebrafish from its toxicity. The results provide insights into the bioremediation of wastewater contaminated 3,5-xylenol.

Novel machine learning models to predict pneumonia events in supratentorial intracerebral hemorrhage populations: An analysis of the Risa-MIS-ICH study.

Background: Stroke-associated pneumonia (SAP) contributes to high mortality rates in spontaneous intracerebral hemorrhage (sICH) populations. Accurate prediction and early intervention of SAP are associated with prognosis. None of the previously developed predictive scoring systems are widely accepted. We aimed to derive and validate novel supervised machine learning (ML) models to predict SAP events in supratentorial sICH populations. Methods: The data of eligible supratentorial sICH individuals were extracted from the Risa-MIS-ICH database and split into training, internal validation, and external validation datasets. The primary outcome was SAP during hospitalization. Univariate and multivariate analyses were used for variable filtering, and logistic regression (LR), Gaussian naïve Bayes (GNB), random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and ensemble soft voting model (ESVM) were adopted for ML model derivations. The accuracy, sensitivity, specificity, and area under the curve (AUC) were adopted to evaluate the predictive value of each model with internal/cross-/external validations. Results: A total of 468 individuals with sICH were included in this work. Six independent variables [nasogastric feeding, airway support, unconscious onset, surgery for external ventricular drainage (EVD), larger sICH volume, and intensive care unit (ICU) stay] for SAP were identified and selected for ML prediction model derivations and validations. The internal and cross-validations revealed the superior and robust performance of the GNB model with the highest AUC value (0.861, 95% CI: 0.793-0.930), while the LR model had the highest AUC value (0.867, 95% CI: 0.812-0.923) in external validation. The ESVM method combining the other six methods had moderate but robust abilities in both cross-validation and external validation and achieved an AUC of 0.843 (95% CI: 0.784-0.902) in external validation. Conclusion: The ML models could effectively predict SAP in sICH populations, and our novel ensemble model demonstrated reliable robust performance outcomes despite the populational and algorithmic differences. This attempt indicated that ML application may benefit in the early identification of SAP.

Conversion Surgery Following Immunochemotherapy in Initially Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma-A Real-World Multicenter Study (RICE-Retro).

Purpose: The present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario. Materials and Methods: In this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared. Results: One hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery. Conclusion: Our results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

LAMP2 as a Biomarker Related to Prognosis and Immune Infiltration in Esophageal Cancer and Other Cancers: A Comprehensive Pan-Cancer Analysis.

Esophageal cancer (ESCA) is a common malignant tumor with poor prognosis. Accumulating evidence indicates an important role of lysosomal-associated membrane protein 2 (LAMP2) in the progression and development of various cancers. In this study, we obtained RNA-sequencing raw count data and the corresponding clinical information for ESCA samples from The Cancer Genome Atlas and Gene Expression Omnibus databases. We comprehensively investigated the expression and prognostic significance of LAMP2 and relationships between LAMP2 expression and prognosis, different clinicopathological parameters, and immune cell infiltration in ESCA. We also obtained the differentially expressed genes between the high LAMP2 expression and low LAMP2 expression groups in ESCA and performed a functional enrichment analysis of the 250 linked genes most positively related to LAMP2 expression. Moreover, we performed the pan-cancer analysis of LAMP2 to further analyze the role of LAMP2 in 25 commonly occurring types of human cancer. We also verified and compared the expression of LAMP2 in 40 samples of human ESCA tissue and adjacent tissues. The results indicated that LAMP2 expression was significantly upregulated in ESCA and various human cancers. In addition, LAMP2 expression was associated with certain clinicopathological parameters, prognosis, and immune infiltration in ESCA and the other types of cancer. Our study represents a comprehensive pan-cancer analysis of LAMP2 and supports the potential use of the modulation of LAMP2 in the management of ESCA and various cancers.

A novel prognostic model: which group of esophageal squamous cell carcinoma patients could benefit from adjuvant chemotherapy.

Background: This study aimed to establish a reliable model for predicting the overall survival (OS) of esophageal squamous cell carcinoma (ESCC) patients and identifying the potential beneficiaries of adjuvant chemotherapy after esophagectomy. Methods: This retrospective study included 819 ESCC patients who underwent esophagectomy as the training cohort. We constructed a prognostic model named GTLN2. Both internal and external validation tests were performed. Potential beneficiaries were defined as ESCC patients who obtained a significantly longer OS after adjuvant chemotherapy. Propensity score matching (PSM) was utilized in the subgroup analysis to screen ESCC beneficiaries of adjuvant chemotherapy. Results: We enrolled a total of 819 cT1b-3 patients in the training cohort. Multiple prognostic factors were associated with adjuvant chemotherapy. Using uni-/multivariate analysis, histological grade (G), tumor invasion depth (T), regional lymph node metastasis (N), and the number of cleared lymph nodes (NCLNs) were identified as independent prognostic factors. Then, we developed the GTLN2 model based on these predictors and validated it using internal calculations [the 1-, 3- and 5-year area under the curves (AUCs) were 0.692, 0.685 and 0.680, respectively; P<0.001] and external cohorts (the 1-, 3-, and 5-year AUCs were 0.651, 0.619 and 0.650, respectively; P<0.001). ESCC patients were categorized into high- and low-risk groups based on their assigned risk scores. After 1:1 patient pairing was performed by PSM in the high-risk group, better OS was noted in patients receiving adjuvant chemotherapy (P=0.024). Conclusions: Differentiating high- and low-risk patient groups via a novel mathematical prediction model allows physicians to identify patients in need of adjuvant chemotherapy accurately.

Investigation of the Cognitive Attitudes and Behaviors of Medical Post-graduates in Clinical Practice During the COVID-19 Pandemic in China.

The cognitive attitudes and behaviors of medical post-graduates may be influenced by the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was used from a questionnaire survey in hospitals affiliated with the Zhejiang University School of Medicine. Questionnaire was distributed online including demographic information, cognitive attitudes, and personal protective behaviors. Moreover, personal protective behaviors such as wearing protective equipment were compared between different academic major and gender, respectively. A total of 176 valid questionnaires were obtained. Of the medical post-graduates in this study, (1) 89.67% believed that the COVID-19 pandemic had an impact on their clinical internships, and 40.34% expressed concerns about their infection on inadequate personal protection; (2) 91.48% took personal protection in hospital and 86.36% enhanced personal hygiene; (3) There were no statistically differences in the personal protection by academic major and gender (p > 0.05). This study suggests that the COVID-19 pandemic had an impact on the medical post-graduates' clinical practice, and affected their cognitive attitudes and behaviors. As such, universities and hospitals should increase pandemic prevention training and investment, provide more psychological counseling to their medical post-graduates to reduce their psychological burden, and take measures to reduce the influence of the COVID-19 pandemic on their medical post-graduates' clinical practice.

Optimal Range of Lymphadenectomy in Pathological Stage T1 and T2 Esophageal Squamous Cell Carcinoma.

BACKGROUND: Lymph node metastasis is a primary contributor to tumor progression in esophageal squamous cell carcinoma (ESCC), and the optimal extent of lymphadenectomy during esophagectomy remains controversial. This study aimed to investigate the appropriate number of lymph nodes to be dissected in pT1-2Nany stage ESCC to achieve the best prognosis and avoid missing positive lymph nodes (PLNs). METHODS: A total of 497 patients with pT1 to pT2 esophageal cancer from two institutions were retrospectively analyzed and their surgical and pathological records were critically reviewed. Stepwise analyses were conducted by calculating a serial of hazard ratios and odd ratios to determine the optimal range of lymphadenectomy for overall survival (OS). RESULTS: The best survival outcome can be obtained when the number of lymph node examined (NLNE) is 10-18 in pT1N0 ESCC, while the NLNE should exceed 24 in pT2N0 diseases. In patients with pT1-2Nany and pT2Nany ESCC, resection of 15-25 and 24-37 lymph nodes, respectively, could provide significant added value for identifying positive nodal metastasis. When the NLNE exceeds this appropriate range, resection of extra lymph node is not helpful to improve the probability of finding PLNs. CONCLUSIONS: For ESCC patients undergoing radical esophagectomy, the optimal extent of lymphadenectomy is 15-25 for pT1Nany disease and 24-37 for pT2Nany disease.

Downregulation of SRPK2 promotes cell cycle arrest though E2F1 in non-small cell lung cancer.

Serine-arginine protein kinase (SRPK) belongs to a class of cell cycle regulating kinases that can phosphorylate proteins containing serine/arginine-Rich (SR) regions. SR proteins are a family of RNA binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. However, little is known about their role in non-small cell lung cancer (NSCLC). In the present study, we found that serine-arginine protein kinase 2 (SRPK2) expression was upregulated in NSCLC tissues compared with adjacent normal tissues. Kaplan-Meier curve analyses showed that the overall survival time of NSCLC patients with high SRPK2 expression was shorter than those with low SRPK2 expression. Overexpression of SRPK2 promoted NSCLC cell proliferation and cell cycle arrest, while knockdown of SRPK2 inhibited proliferation and promoted cell cycle arrest in NSCLC cell lines. SRPK2 promoted the transcriptional regulation of E2F1 on downstream cell cycle related genes through phosphorylation of SC35. Xenograft model showed that SRPK2 promoted tumor growth in vivo. SRPK2 phosphorylated SC35 and phosphorylated SC35 activated E2F1 transcription of cyclin-related proteins, thereby promoting the cycle progression of NSCLC. Our findings demonstrated that SRPK2 may be a potential therapeutic target for NSCLC clinical therapy, which plays an important role in the progression of NSCLC.

Differential responses of stressful elements to predatory exposure in behavior-lateralized mice.

BACKGROUND: Predatory stress as a psychological stressor can elicit the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is involved in the dialogue of the neuroimmunoendocrine network. The brain has been proven to regulate the activity of the HPA axis by way of lateralization. In the present study, we probed the pivotal elements of the HPA circuitry including CRH, GR and a multifunctional cytokine in behavior-lateralized mice to determine their changes when the animals were subjected to predator exposure. METHODS: Behavior-lateralized mice were classified into left-pawed and right-pawed mice through a paw-preference test. Thereafter, mice in the acute stress group received a single 60-min cat exposure, and mice in the chronic group received daily 60-min cat exposure for 14 consecutive days. The plasma CS and TNF-α were determined by ELISA, the hypothalamic CRH mRNA and hippocampal GR mRNA were detected by real-time PCR, and the hippocampal GR protein was detected by western blot analysis. RESULTS: The results revealed that the levels of plasma CS were significantly elevated after chronic predatory exposure in both right-pawed and left-pawed mice; the right-pawed mice exhibited a higher plasma CS level than the left-pawed mice. Similarly, the acute or chronic cat exposure could induce the release of plasma TNF-α, and the left-pawed mice tended to show a higher level after the acute stress. Chronic stress significantly upregulated the expression of hypothalamic CRH mRNA in both left-pawed and right-pawed mice. Normally, the left-pawed mice exhibited a higher GR expression in the hippocampus than the right-pawed mice. After the cat exposure, the expression of GR in both left-pawed and right-pawed mice was revealed to be greatly downregulated. CONCLUSION: Our findings indicate that predatory stress can invoke a differential response of stressful elements in behavior-lateralized mice. Some of these responses shaped by behavioral lateralization might be helpful for facilitating adaption to various stimuli.

LPS-Primed Release of HMGB-1 from Cortical Astrocytes is Modulated Through PI3K/AKT Pathway.

Studies have shown that LPS-preconditioned tolerant state could protect against brain injury to subsequent challenges. We hypothesized astrocytes were directly involved in the readjustment to confer neuroprotective effects with LPS pretreatment. High-mobility group box 1(HMGB-1) from LPS-preconditioned astrocytes, presumably serving as a positive regulator, might contribute to the favorable preconditioned effects. Furthermore, a potential cellular pathway (PI3K/AKT pathway), has been proposed for the active regulation of LPS-primed reactive astrocytes to secrete HMGB-1. In the present study, we used a low concentration of LPS to directly prime the astrocytes in vitro, and the subsequent astrocytic reactions, including cytokine secretion, the expression of transcription factors, and the release of HMGB-1 were examined after the blockade of the PI3K pathway. The data showed that LPS preconditioning could reduce some capacity of astrocytes to subsequent challenge in vitro. PI3K/AKT pathway was partially involved in the modulation of the release HMGB-1 from reactive astrocytes. These findings offer direct evidence supporting the flexible roles of astrocytes in mediating LPS-primed neuroprotection, and highlight additional targets for future attempts to modify the protective effects of astrocytes through LPS preconditioning.