Comparative Transcriptomic Analyses Propose the Molecular Regulatory Mechanisms Underlying 1,8-Cineole from Cinnamomum kanehirae Hay and Promote the Asexual Sporulation of Antrodia cinnamomea in Submerged Fermentation.

Antrodia cinnamomea is a valuable edible and medicinal mushroom with antitumor, hepatoprotective, and antiviral effects that play a role in intestinal flora regulation. Spore-inoculation submerged fermentation has become the most efficient and well-known artificial culture process for A. cinnamomea. In this study, a specific low-molecular compound named 1,8-cineole (cineole) from Cinnamomum kanehirae Hay was first reported to have remarkably promoted the asexual sporulation of A. cinnamomea in submerged fermentation (AcSmF). Then, RNA sequencing, real-time quantitative PCR, and a literature review were performed to predict the molecular regulatory mechanisms underlying the cineole-promoted sporulation of AcSmF. The available evidence supports the hypothesis that after receiving the signal of cineole through cell receptors Wsc1 and Mid2, Pkc1 promoted the expression levels of rlm1 and wetA and facilitated their transfer to the cell wall integrity (CWI) signal pathway, and wetA in turn promoted the sporulation of AcSmF. Moreover, cineole changed the membrane functional state of the A. cinnamomea cell and thus activated the heat stress response by the CWI pathway. Then, heat shock protein 90 and its chaperone Cdc37 promoted the expression of stuA and brlA, thus promoting sporulation of AcSmF. In addition, cineole promoted the expression of areA, flbA, and flbD through the transcription factor NCP1 and inhibited the expression of pkaA through the ammonium permease of MEP, finally promoting the sporulation of AcSmF. This study may improve the efficiency of the inoculum (spores) preparation of AcSmF and thereby enhance the production benefits of A. cinnamomea.

Advantages of McKeown minimally invasive oesophagectomy for the treatment of oesophageal cancer: propensity score matching analysis of 169 cases.

BACKGROUND: Oesophagectomy, the gold standard for oesophageal cancer treatment, causes significantly high morbidity and mortality. McKeown minimally invasive oesophagectomy (MIE) is preferred for treating oesophageal malignancies; however, limited studies with large sample sizes focusing on the surgical and oncological outcomes of this procedure have been reported. We aimed to compare the clinical safety and efficacy of McKeown MIE with those of open oesophagectomy (OE). PATIENTS AND METHODS: Overall, 338 oesophageal cancer patients matched by gender, age, location, size, and T and N stages (McKeown MIE: 169 vs OE: 169) were analysed. The clinicopathologic features, operational factors, postoperative complications, and prognoses were compared between the groups. RESULTS: McKeown MIE resulted in less bleeding (200 mL vs 300 mL, p<0.01), longer operation time (335.0 h vs 240.0 h, p<0.01), and higher number of harvested lymph nodes (22 vs 9, p<0.01) than OE did. Although the rate of recurrent laryngeal nerve injury in the two groups was not significantly different, incidence of anastomotic leakage (8 vs 24, p=0.003) was significantly lower in the McKeown MIE group. In addition, patients who underwent McKeown MIE had higher 5-year overall survival than those who underwent OE (69.9% vs 40.4%, p<0.001). CONCLUSION: McKeown MIE is proved to be feasible and safe to achieve better surgical and oncological outcomes for oesophageal cancer compared with OE.

Addiction Symptom Network of Young Internet Users: Network Analysis.

BACKGROUND: An increasing number of people are becoming addicted to the internet as a result of overuse. The Internet Addiction Test (IAT) is a popular tool for evaluating internet use behaviors. The interaction between different symptoms and the relationship between IAT and clinical diagnostic criteria are not well understood. OBJECTIVE: This study aimed to explore the core symptoms of internet addiction (IA) and the correlation between different symptoms of the IA symptom network. Network analysis was also conducted to explore the association between the IAT scale and the Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) criteria for IA. METHODS: We recruited 4480 internet users (aged 14-24 years), and they completed the IAT. The final analysis included 63.50% (2845/4480) of the participants after screening the submitted questionnaires. Participants were classified into IA group and non-IA (NIA) group. By using partial correlation with Lasso regularization networks, we identified the core symptoms of IA in each group and compared the group differences in network properties (strength, closeness, and betweenness). Then, we analyzed the symptom networks of the DSM-5 diagnostic criteria and IAT scale for IA. RESULTS: A total of 12.47% (355/2845) of the patients were in the IA group and 87.52% (2490/2845) of the patients were in the NIA group, and both groups were evaluated for the following nodes: IAT_06 (school work suffers; strength=0.511), IAT_08 (job performance suffers; strength=0.531), IAT_15 (fantasize about being on the web; strength=0.474), IAT_17 (fail to stop being on the web; strength=0.526), and IAT_12 (fear about boredom if offline; strength=0.502). The IA groups had a stronger edge between IAT_09 (defensive or secretive about being on the web) and IAT_18 (hidden web time) than the NIA groups. The items in DSM-5 had a strong association with IAT_12 (weight=-0.066), IAT_15 (weight=-0.081), IAT_17 (weight=-0.106), IAT_09 (weight=-0.198), and IAT_18 (weight=-0.052). CONCLUSIONS: The internet use symptom network of the IA group is significantly different from that of the NIA group. Nodes IAT_06 (school work affected) and IAT_08 (work performance affected) are the resulting symptoms affected by other symptoms, whereas nodes IAT_12 (fear about boredom if offline), IAT_17 (inability to stop being on the web), and IAT_15 (fantasize about being on the web) are key symptoms that activate other symptoms of IA and are strongly linked to the inability to control the intention to play games in the DSM-5.

Prognostic Factors for Primary Localized Gastrointestinal Stromal Tumors After Radical Resection: Shandong Gastrointestinal Surgery Study Group, Study 1201.

BACKGROUND: Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. METHODS: Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. RESULTS: Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8-95.4), 85.9% (95% CI 84.7-87.1), and 78.8% (95% CI 77.0-80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count < 6 per 50 high-power fields [HPFs]) + 1.442 (tumor mitotic count between 6 and 10 per 50 HPFs) + 2.026 (tumor mitotic count > 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. CONCLUSIONS: Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

Normothermic extracorporeal membrane oxygenation support: Improving the function of intestinal grafts obtained from cardiac death donors.

Extracorporeal membrane oxygenation (ECMO) could ameliorate the energy status and viability of bowel grafts from cardiac death donors. However, the function of these grafts after transplantation is not clear. The purpose of the study was to evaluate the early function of intestinal grafts after transplantation from expected cardiac death donors supported with normothermic extracorporeal support using a porcine allogeneic orthotopic segmental small bowel transplantation model. Eighteen domestic crossbred donor pigs were assigned to living donation (LD), donation after cardiac death (DCD), and ECMO groups. In the LD group, small bowels were harvested and preserved immediately in cold storage. In the other two groups, the donor pigs received conventional rapid recovery treatment or 1-hour normothermic extracorporeal support after 10-minutes expected cardiac arrest. Subsequently, the small bowels were removed and preserved in cold storage. After 5-6 hours of preservation, small bowel grafts were transplanted into the recipient pigs that underwent enterectomy. The pathology and electron microscopy results, cell apoptosis rate, tight junction protein expression level in the intestinal mucosa, and plasma endotoxin level were evaluated after transplantation. All grafts functioned on the basis of the maltose absorption test results at day 7 after transplantation. There were no significant differences in the morphological changes in the intestinal mucosa among the three groups at day 7 after transplantation. The cell apoptosis rate and plasma endotoxin level in the ECMO group did not differ significantly than those in the LD group, but were evidently lower than those in the DCD group (P < .001). The intestinal absorptive function improved significantly in the ECMO group in contrast with that in the DCD group (P < .001). Short-term ECMO intervention can alleviate ischemia-reperfusion injuries in intestinal grafts and improve intestinal absorptive function in the early stage after transplantation. Reducing caspase-3 protein expression and cell apoptosis in the intestinal mucosa may be one of the protective mechanisms of ECMO intervention.

Air-Tolerant Direct Thiol Esterification with Carboxylic Acids Using Hydrosilane via Simple Inorganic Base Catalysis.

Direct thioesterification of carboxylic acids with thiols using nontoxic activation agents is highly desirable. Herein, an efficient and practical protocol using safe and inexpensive industrial waste polymethylhydrosiloxane as the activation agent and K3PO4 with 18-crown-6 as a catalyst is described. Various functional groups on carboxylic acid and thiol substituents can be tolerated by the present system to afford thioesters in yields of 19-100%.

Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon cancer cell line SW480 for apoptosis induction.

The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.

Intestinal Conditioning After Cardiac Arrest: The Use of Normothermic Extracorporeal Membrane Oxygenation in the Non-Heart-Beating Animal Model.

The effect of normothermic extracorporeal membrane oxygenation (NECMO) on small bowel preservation in a clinically relevant large animal model of expected donation after cardiac death (eDCD) was evaluated. Thirty domestic crossbred donor pigs were divided into five groups. The first group served as the live donation (LD) group, the second group served as the donation after cardiac death (DCD) group, and the remaining were further assigned into three subgroups: E1 group (1 h NECMO support), E3 group (3 h NECMO support), and E5 group (5 h NECMO support). Pathology, electron microscopy, energy metabolism, cell apoptosis, and tight junction (TJ) protein expression level of intestinal mucosa and the level of plasma d-lactic acid were evaluated in normal, cardiac death and at the end of extracorporeal support, respectively. The mean arterial pressure and PaO2 were maintained over 60 and 267 mm Hg during NECMO support, respectively. One hour of extracorporeal support could improve the energy status in intestines of the DCD group. Although the histologic damage and apoptosis of the E1 group had no significant difference with those of the LD and DCD groups (P > 0.05), the levels of intestinal mucosa TJ protein decreased (P < 0.05), and plasma d-lactic acid increased progressively (P < 0.05). With the extension of extracorporeal support, the degree of intestinal mucosa damage and intestinal permeability gradually increased, as well as the content of adenosine triphosphate in intestinal mucosa. The normothermic extracorporeal support for 1 h in DCD is beneficial for improving the energy status and viability of the bowel. However, the integrity of intestinal mucosa was destroyed gradually as extracorporeal support time went by. And the activation of intestinal epithelial apoptosis and hyperoxia might be the factors that lead to intestinal mucosa injury.

Characterization of the withdrawal phase in a swine controlled intestinal donation after circulatory death model.

PURPOSE: Transplantation of donation after cardiac death (DCD) intestine has higher rates of organ failure and complications. Fortunately, this is less grievous in a subclass of DCD called controlled (CDCD), those with irreversible but incomplete brain injury. The aim of the paper is to establish a CDCD porcine model which is closely mimicking human CDCD scenario, and investigate the physiologic changes from withdrawal of ventilatory support to circulatory arrest. METHOD: Ten domestic crossbred pigs were anesthetized and ventilated with room air. Once all baseline data was taken, atracurium besilate (0.9 mg/kg, 3×ED95) was administered and the ventilator was discontinued while the animal was under deep anesthesia to establish the porcine CDCD model. Meanwhile, heparin (150~200 U/kg) was administered after discontinuation of the ventilator. The time to death and the changes of arterial blood gases and hemodynamic parameters were monitored every 5 minutes until circulatory arrest. In addition, histopathology, ultrastructures (via electron microscope) and expression of tight junction proteins of intestinal mucosa were observed at the baseline and the time of death. RESULT: The mean time to death was approximately (21.8±3.12 min. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Systolic blood pressure and heart rate quickly increased to 118.5±10.4 mmHg and 108.2±4.94 bpm, respectively. Blood pressure and heart rate then reduced rapidly until circulatory arrest. Moreover, the PaO2 quickly dropped to 17.4±3.13 mmHg, the blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. In addition, warm ischemia damaged intestinal mucosa and reduced TJ proteins expression. CONCLUSION: A new swine CDCD model, simulating three stages of "withdrawal of ventilation, systemic anticoagulation and determination of death", which closely mimics the human DCD scenario and can thus be used in studies related to organ transplantation, was successfully established.

Elevated polyclonal IgG4 mimicking a monoclonal gammopathy in IgG4-related disease-a case-based review.

IgG4-related diseases (IgG-RDs) are a group of fibroinflammatory diseases that affect a variety of tissues, resulting in tumour-like effects and/or organ dysfunction. Monoclonal gammopathies (MGPs) are a group of disorders characterized by clonal proliferation of plasma cells or lymphoid cells resulting in the secretion of a monoclonal immunoglobulin. Cases of MGPs in IgG4-RDs coexisting with plasma cell dyscrasias and lymphoid neoplasms have been reported over the past few years. Therefore, the results of examinations of M protein in IgG4-RD patients should be interpreted with caution. Herein, we report the case of a 58-year-old male with a history of type 2 diabetes who presented with submandibular masses, anosmia, swollen lymph nodes, proteinuria, and renal impairment. Laboratory tests revealed hyperglobulinemia and elevated levels of IgG4 (124 g/L) and serum-free light chains (sFLCs). Serum protein electrophoresis (SPEP) revealed an M spike of 5.6 g/dL, and immunofixation electrophoresis (IPE) revealed biclonal IgG-κ and IgG-λ. The patient underwent bone marrow, lymph node, and kidney biopsy, which ruled out plasma cell disorders and lymphoma. He was finally diagnosed with an IgG4-RD comorbid with diabetic nephropathy. The findings in this case highlight that significant activation of B cells in IgG4-RD patients, especially those with multiorgan involvement can lead to significant hyperglobulinemia and high sFLC and IgG4 levels, which are more pronounced in the setting of renal impairment. Relatively high concentrations of polyclonal IgG4 can give rise to a focal band bridging the ß and γ fractions, which may mimic the appearance of a monoclonal band on SPEP and monoclonal gammaglobulinemia in IFE. The patient experienced considerable improvement in his symptoms after rituximab combined with glucocorticoid therapy, and a monoclonal immunoglobulin was not detected.

Prognostic value of preoperative white blood cell to hemoglobin ratio and fibrinogen to albumin ratio in patients with colorectal cancer.

The prognostic value of preoperative white blood cell to hemoglobin ratio (WHR) and fibrinogen to albumin ratio (FAR) in colorectal cancer (CRC) is unknown. The purpose of this study was to analyze the correlation between preoperative WHR and FAR and the prognosis of CRC patients. The retrospective study analyzed the medical records of 207 patients with colorectal cancer who were admitted to Linyi People's Hospital between June 1, 2017 and June 1, 2021. The receiver operator curve was used to determine the cutoff value of 4.604 for WHR and 0.086 for FAR, and the patients were divided into high and low groups for comparative analysis of clinical data. Cox proportional hazards regression models were used to assess independent risk factors for disease-free survival (DFS) and overall survival (OS) in univariate and multifactorial analyses. Kaplan-Meier methods were used for survival analysis and logrank tests were used to assess survival differences. Multifactorial Cox analysis showed that tumor pathological stage (HR = 6.224, 95% CI:3.063-12.647, P < .001), and WHR (HR = 3.681, 95% CI:1.768-7.401, P < .001) were the independent risk factors for DFS in CRC patients. Tumor pathological stage (HR = 4.080, 95% CI:1.992-8.360, P < .001), and WHR (HR = 3.397, 95% CI:1.662-6.940, P = .001) were independent risk factors for OS. High levels of WHR and high levels of FAR were associated with lower DFS (P < .001) and OS (P < .001).CRC patients with both higher WHR and FAR had significantly lower DFS (P < .001) and OS (P < .001). DFS and OS may be shorter in CRC patients with high WHR and high FAR, perhaps associated with poor prognosis in CRC patients, and WHR and FAR may be potential CRC prognostic markers.

Vaccine confidence mediates the association between a pro-social pay-it-forward intervention and improved influenza vaccine uptake in China: A mediation analysis.

INTRODUCTION: A Chinese clinical trial has demonstrated that a prosocial pay-it-forward intervention that offered subsidized vaccination and postcard messages effectively increased influenza vaccine uptake and vaccine confidence. This secondary analysis explored the potential mediating role of vaccine confidence on the association between a pay-it-forward intervention and influenza vaccine uptake, and how this might vary by individual annual income levels. METHODS: Data from 300 participants (150 standard-of-care and 150 pay-it-forward participants) were included in the analysis. We conducted descriptive analysis of demographic and vaccine confidence variables. Multivariable regression and mediation analysis on interventions, vaccine confidence and vaccine uptake were conducted. A sub-group analysis was conducted to further understand whether associations between these variables vary by income levels (<=$1860 or >$1860). RESULTS: The pay-it-forward intervention was significantly associated with greater levels of perceived influenza vaccine importance (adjusted odds ratio (aOR) = 3.60, 95 %CI: 1.77-7.32), effectiveness (aOR = 3.37, 95 %CI: 1.75-6.52) and safety (aOR = 2.20, 95 %CI: 1.17-4.15). Greater perceived influenza vaccine importance was associated with increased vaccine uptake (aOR = 8.51, 95 %CI: 3.04-23.86). The indirect effect of the pay-it-forward intervention on vaccination was significant through improved perceived influenza vaccine importance (indirect effect1 = 0.07, 95 %CI: 0.02-0.11). This study further revealed that, irrespective of the individual income level, the pay-it-forward intervention was associated with increased vaccine uptake when compared to the standard-of-care approach. CONCLUSIONS: Pay-it-forward intervention may be a promising strategy to improve influenza vaccine uptake. Perceived confidence in vaccine importance appears to be a potential mediator of the association between pay-it-forward and vaccine uptake.

3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: synthesis, molecular docking and antibacterial evaluation.

Thirty-eight 3-aryl-4-acyloxyethoxyfuran-2(5H)-ones were designed, prepared and tested for antibacterial activities. Some of them showed significant antibacterial activity against Gram-positive organism, Gram-negative organism and fungus. Out of these compounds, 4-(2-(3-chlorophenylformyloxy)ethoxy)-3-(4-chlorophenyl)furan-2(5H)-one (d40) showed the widest spectrum of activity with MIC50 of 2.0µg/mL against Staphylococcus aureus, 4.3µg/mL against Escherichia coli, 1.5µg/mL against Pseudomonas aeruginosa and 1.2µg/mL against Candida albicans. Our data disclosed that MIC50 values against whole cell bacteria are positive correlation with MIC50 values against tyrosyl-tRNA synthetase. Meanwhile, molecular docking of d40 into S. aureus tyrosyl-tRNA synthetase active site was also performed, and the inhibitor tightly fitting the active site might be an important reason why it has high antimicrobial activity.

Modified transumbilical laparoscopic cholecystectomy: double-incision, triple-port access.

Transumbilical laparoscopic cholecystectomy has been increasingly performed in recent years, using special access devices and instruments through one incision in the umbilicus. We have modified the technique by using a two-incision triple-port access approach and conventional laparoscopic instruments. A total of 52 patients accepted the modified transumbilical laparoscopic cholecystectomy, and all the procedures were completed successfully. The operative time was 150 minutes for the first case, 100 minutes and 90 minutes for the second and third cases, and an average of 50 ± 14 minutes for the following 49 cases. All patients were discharged on post-operative day 3. No complications were observed during a follow-up of at least three months. The umbilical incisions were nearly invisible, and all patients were satisfied with the abdominal cosmetic results.In conclusion, transumbilical laparoscopic cholecystectomy using a double-incision triple-port access approach and conventional laparoscopic instruments as described in this study is safe and feasible, and it reduces the conflict of instruments without using special devices.

KLF4 suppresses the proliferation of perihilar cholangiocarcinoma by negatively regulating GDF15 and phosphorylating AKT.

Krüppel­like factor 4 (KLF4) is a transcription factor which functions as a tumor suppressor or an oncogene in numerous types of solid tumors. However, its expression levels and function in perihilar cholangiocarcinoma (pCCA) have yet to be elucidated. In the present study, in order to investigate its roles in pCCA, reverse transcription­quantitative PCR (RT­qPCR), western blot analysis and immunohistochemistry were used to detect KLF4 expression in pCCA. The Chi­squared test was used to analyze the associations between KLF4 and the clinicopathological features of patients with pCCA. Univariate and multivariate analyses were subsequently used to analyze the prognostic significance of KLF4. The tumor suppression of KLF4 was investigated for the purposes of illustrating its biological function both in vitro and in vivo. Furthermore, the association between KLF4 and growth/differentiation factor 15 (GDF15) was determined using pCCA tissue microarray (TMA) analysis and RT­qPCR. The underlying molecular mechanisms between KLF4 and GDF15 were subsequently investigated in vitro. In pCCA tissues, KLF4 was found to be downregulated, and this was negatively associated with the histological grade and tumor size. The knockdown of KLF4 was also found to be a prognostic indicator of the poorer survival of patients with pCCA. Based on in vitro and in vivo analyses, KLF4 was found to suppress tumor progression and induce cell apoptosis. Furthermore, it was found that KLF4 executed its tumor suppressive effects via the regulation of the GDF15/AKT signaling pathway. Taken together, the findings of the present study demonstrate that KLF4 may be considered as an independent biomarker of a favorable prognosis of patients with pCCA, and the KLF4/GDF15/AKT signaling pathway may potentially be a novel molecular therapeutic target for patients with pCCA.

Identification of potential biomarkers for colorectal cancer by clinical database analysis and Kaplan-Meier curves analysis.

This study aimed to explore critical genes as potential biomarkers for the diagnosis and prognosis of colorectal cancer (CRC) for clinical utility. To identify and screen candidate genes involved in CRC carcinogenesis and disease progression, we downloaded microarray datasets GSE89076, GSE73360, and GSE32323 from the GEO database identified differentially expressed genes (DEGs), and performed a functional enrichment analysis. A protein-protein interaction network was constructed, and correlated module analysis was performed using STRING and Cytoscape. The Kaplan-Meier survival curve shows the survival of the hub genes. The expression of cyclin-dependent kinase (CDK1), cyclin B1 (CCNB1), and PCNA in tissues and changes in tumor grade were analyzed. A total of 329 DEGs were identified, including 264 upregulated and 65 downregulated genes. The functions and pathways of DEGs include the mitotic cell cycle, poly(A) RNA binding replication, ATP binding, DNA replication, ribosome biogenesis in eukaryotes, and RNA transport. Forty-seven Hub genes were identified, and biological process analysis showed that these genes were mainly enriched in cell cycle and DNA replication. Patients with mutations in CDK1, PCNA, and CCNB1 had poorer survival rates. CDK1, PCNA, and CCNB1 were significantly overexpressed in the tumor tissues. The expression of CDK1 and CCNB1 gradually decreased with increasing tumor grade. CDK1, CCNB1, and PCNA can be used as potential markers for the diagnosis and prognosis of CRC. These genes are overexpressed in colon cancer tissues and are associated with low survival rates in CRC patients.

Prognostic modeling of overall survival and analysis of K-M survival curves in patients with primary colon cancer: A SEER-based study.

This study aimed to establish a validated prognostic survival column line chart by analyzing data from patients with colon cancer (CC) in the SEER database. The nomogram proposed in this study was based on the retrospective data of patients diagnosed with CC in the SEER database from 1975 to 2015. Randomly divided into training and validation sets, the nomogram was constructed using the Cox model, and the discriminatory power of the nomogram and its predictive accuracy were determined using the consistency index and associated calibration curves. In a multifactorial analysis of the main cohort, the independent factors for survival were age, sex, race, tumor stage, and tumor grade, all of which were included in the nomogram and were prognostic factors for patients with CC (P < .05). The calibration curve of the survival probability showed good agreement between the prediction of the nomogram and the actual observation. The validation calibration curve showed good correlation and agreement between predicted and observed values. Multifactorial analysis showed that the factors affecting the prognosis of patients with CC included age, sex, race, tumor-node-metastasis stage, and tumor pathological stage. The nomogram prediction model proposed in this study has high accuracy and can provide more accurate prognostic prediction and relevant reference values for assessing the postoperative survival of CC patients and guiding clinical decision-making.

Network analysis of internet addiction and sleep disturbance symptoms.

BACKGROUND: Internet addiction (IA) is a behavioral addiction to problematic internet use. IA is associated with poorer sleep quality. Few studies to date, however, have explored the interactions between symptoms of IA and symptoms of sleep disturbance. This study uses network analysis to identify bridge symptoms by analyzing these interactions in a large sample of students. METHOD: We recruited 1977 university students to participate in our study. Each student completed the Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI). We used these collected data for network analysis to identify the bridge symptoms in the IAT-PSQI network by calculating the bridge centrality. Furthermore, the closest symptom connected with the bridge symptom was found to identify the comorbidity mechanisms. RESULTS: The core symptom of IA and the sleep disturbance network was "I08" (Study efficiency suffers due to internet use). The bridge symptoms between IA and sleep disturbance were "I14" (Surfing the internet late instead of sleeping), "P_DD" (Daytime dysfunction), and "I02" (Spending much time online instead of socializing in real life). Among the symptoms, "I14" had the highest bridge centrality. The edge connecting nodes "I14" and "P_SDu" (Sleep duration) had the strongest weight (0.102) around all the symptoms of sleep disturbance. Nodes "I14" and "I15" (Thinking about online shopping, games, social networking, and other network activities when unable to access the internet) had the strongest weight (0.181), connecting all the symptoms of IA. CONCLUSIONS: IA leads to poorer sleep quality, most likely by shortening sleep duration. Preoccupation with and craving the internet while being offline may lead to this situation. Healthy sleep habits should be learned, and craving may be a good point at which to treat the symptoms of IA and sleep disturbance.

Gender difference in network relationship between inter-temporal decisions and prefrontal activation levels in internet gaming disorder.

Background: Impulsivity and decision-making are key factors in addiction. However, little is known about how gender and time sensitivity affect impulsivity in internet gaming disorder (IGD). Objective: To investigate the gender difference of impulsive decision-making and relevant brain responses in IGD. Methods: We conducted a functional magnetic resonance imaging (fMRI) study with 123 participants, including 59 IGD individuals (26 females) and 64 matched recreational game users (RGUs, 23 females). Participants performed a delay-discounting task during fMRI scanning. We examined gender-by-group effects on behavioral and neural measures to explore the preference for immediate over delayed rewards and the associated brain activity. We also investigated the network correlations between addiction severity and behavioral and neural measures, and analyzed the mediating role of brain activity in the link between delay discounting parameters and IGD severity. Results: We found significant gender-by-group interactions. The imaging results revealed gender-by-group interactions in the dorsolateral prefrontal cortex, medial frontal gyrus, and inferior frontal gyrus (IFG). Post hoc analysis indicated that, for females, RGUs showed higher activity than IGD individuals in these brain regions, while for males IGD individuals exhibited higher activity than RGUs. The activation in the left IFG mediated the relation between Internet Addiction Test score and discount rate in females. In males, the activation in the right dlPFC mediated the relation between IAT score and time sensitivity. Discussion: Our findings imply that male IGD participants demonstrate impaired intertemporal decisions associated with neural dysfunction. Influencing factors for impulsive decision-making in IGD diverge between males (time sensitivity) and females (discount rate). These findings augment our comprehension of the neural underpinnings of gender differences in IGD and bear significant implications for devising effective intervention strategies for treating people with IGD.

p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis.

BACKGROUND: To analyze the p42.3 gene expression in gastric cancer (GC) cell, find the relationship between protein structure and function, establish the regulatory network of p42.3 protein molecule and then to obtain the optimal regulatory pathway. METHODS: The expression of p42.3 gene was analyzed by RT-PCR, Western Blot and other biotechnologies. The relationship between the spatial conformation of p42.3 protein molecule and its function was analyzed using bioinformatics, MATLAB and related knowledge about protein structure and function. Furthermore, based on similarity algorithm of spatial layered spherical coordinate, we compared p42.3 molecule with several similar structured proteins which are known for the function, screened the characteristic nodes related to tumorigenesis and development, and established the multi variable relational model between p42.3 protein expression, cell cycle regulation and biological characteristics in the level of molecular regulatory networks. Finally, the optimal regulatory network was found by using Bayesian network. RESULTS: (1) The expression amount of p42.3 in G1 and M phase was higher than that in S and G2 phase; (2) The space coordinate systems of different structural domains of p42.3 protein were established in Matlab7.0 software; (3) The optimal pathway of p42.3 gene in protein regulatory network in gastric cancer is Ras protein, Raf-1 protein, MEK, MAPK kinase, MAPK, tubulin, spindle protein, centromere protein and tumor. CONCLUSION: It is of vital significance for mechanism research to find out the action pathway of p42.3 in protein regulatory network, since p42.3 protein plays an important role in the generation and development of GC.