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Quan Zhou,* Chao-Nan Hou,* Huai-Jie Yang,* Ze He, Man-Zhen Zuo Department of Gynecology and Obstetrics, The People’s Hospital of China Three Gorges University/The First People’s Hospital of Yichang, Yichang 443000, China *These authors contributed equally to this work Background: Increased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated.Materials and methods: In the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis , Kaplan–Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery.Results: It was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis.Conclusion: These results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment. Keywords: EGFR, ovarian cancer, database mining, prognostic value, bioinformatics analysis

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2023. Published by Elsevier B.V.)

This study evaluates the management capacity ability and profitable capacity of eight public-private partnership hospitals in Taiwan from 2015 to 2020. By conducting various ratio analyses of the financial statement, this study found these hospitals have achieved a balance between management efficiency and profitability, thereby confirming the viability of the PPP model for hospital management. In addition, the subject hospitals play a vital role as isolation hospitals during the COVID-19 pandemic. Beyond offering medical assistance to infected individuals, these hospitals contribute to the integrity of Taiwan's medical network, mitigating the impact of the pandemic. Overall, establishing and managing hospitals with PPP partnership is a feasible solution as it alleviates governmental financial burdens related to medical welfare and achieves profitability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The cortex (i.e., absorptive tissue) and stele (transportive vascular tissue) are fundamental to the function of plant roots. Unraveling how these anatomical structures are assembled in absorptive roots is essential for our understanding of plant ecology, physiology, and plant responses to global environmental changes. In this review, we first compile a large data set on anatomical traits in absorptive roots, including cortex thickness and stele radius, across 698 observations and 512 species. Using this data set, we reveal a common root allometry in absorptive root structures, i.e., cortex thickness increases much faster than stele radius with increasing root diameter (hereafter, root allometry). Root allometry is further validated within and across plant growth forms (woody, grass, and liana species), mycorrhiza types (arbuscular mycorrhiza, ectomycorrhiza, and orchid mycorrhizas), phylogenetic gradients (from ferns to Orchidaceae), and environmental change scenarios (e.g., elevation of atmospheric CO 2 concentration and nitrogen fertilization). These findings indicate that root allometry is common in plants. Importantly, root allometry varies greatly across species. We then summarize recent research on the mechanisms of root allometry and potential issues regarding these mechanisms. We further discuss ecological and evolutionary implications of root allometry. Finally, we propose several important research directions that should be pursued regarding root allometry., Competing Interests: We declare that we have no conflict interest., (© 2023 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

To compare the potential influences of blind insertion and up-down optimized glottic exposure manoeuvre on the oropharyngeal leak pressure (OPLP) in using SaCoVLM™ video laryngeal mask (VLM) among patients undergoing general anesthesia. A randomized self-control study controlled was conducted to investigate the effect of two insertion techniques on OPLP. A total of 60 patients (male or female, 18-78 years, BMI 18.0-30.0 kg m -2 and ASA I-II) receiving selective surgery under general anesthesia were randomly recruited. After induction of anesthesia, the SaCoVLM™ was inserted by blind insertion manoeuvre. The glottic exposure grading(V1) of the SaCoVLM™ visual laryngeal mask and the OPLP(P1) were recorded. And the glottic exposure grading(V2) and OPLP(P2) of SaCoVLM™ were recorded again when the glottic exposure grading was optimal. The glottis exposure grading and OPLP were compared before and after different insertion manoeuver. The glottic exposure grading (V2) obtained by using up-down optimized glottic exposure manoeuvre was better than that obtained by using blind insertion manoeuvre (V1)(P < 0.001). The OPLP was significantly lower in the blind insertion manoeuvre (P1) than in the up-down optimized glottic exposure manoeuvre (P2) (32.4 ± 5.0 cmH 2 O vs. 36.3 ± 5.2 cmH 2 O, P < 0.001). In using SaCoVLM™, higher OPLP and better glottic exposure grading were achieved through up-down optimized glottic exposure manoeuvre, protecting the airway while real-time monitoring of conditions around the glottis, which significantly improves airway safety. Our results suggests that up-down optimized glottic exposure manoeuver may be a useful technique for SaCoVLM™ insertion.Trial registration: ChiCTR, ChiCTR2000028802. Registered 4 January 2020, http://www.chictr.org.cn/ChiCTR2000028802., (© 2022. The Author(s).)

Runt-related transcription factor 3 (RUNX3) plays a pivotal role in tumor microenvironment and immune infiltration. However, the prognostic and immunological roles of RUNX3 in pancancer remain unclear. In the current study, we explored the expression profiles, prognostic landscape, and immune infiltration of RUNX3 in pancancer through a variety of online platforms, including HPA, ONCOMINE, UALCAN, GEPIA, PrognoScan, TCGA, TIMER, R2, and Reactome databases. In general, RUNX3 was widely expressed in tonsil, gallbladder, skin, spleen, lymph node, and bone marrow, and RUNX3 was frequently higher expression in tumor tissues compared to normal tissues. In prognostic analysis, the RUNX3 expression level was significantly correlated with the clinical outcomes of bladder cancer, blood cancer, brain cancer, breast cancer, colorectal cancer, lung cancer, and ovarian cancer. In mutation analysis, a total 72 mutation sites were located within amino acids 1 to 415 of RUNX3, including 65 missense sites and seven truncating sites, whereas the mutation frequency of skin cutaneous melanoma and uterine corpus endometrial carcinoma (UCEC) is relatively high (> 3%). In immune infiltration analysis, the RUNX3 expression level was significantly related to recognized markers and the immune infiltration levels of various types of immune cells in colon adenocarcinoma (COAD) and brain lower grade glioma (LGG). After that, 453 RUNX3 co-expressed genes were recognized in COAD, lymphoid neoplasm diffuse large B-cell lymphoma, LGG, and ovarian serous cystadenocarcinoma (OV). Pathway enrichment analysis revealed that RUNX3 co-expressed genes were remarkably enriched in immune system and tumor progression pathways. RUNX3 expression is associated with clinical prognosis, immune infiltration, and identified RUNX3 related pathways in a variety of tumors, which may serve as targets of promising prognostic markers and novel therapeutic targets for various human cancers.

Background: When a difficult airway is unanticipatedly encountered and the initial laryngoscopic intubation fails, a supraglottic airway device (SAD) may be placed to aid ventilation and oxygenation, and act as a conduit for intubation. SaCoVLM™, as new SAD, can offer a direct vision to guide intubation. However, no study has evaluated the performance of SaCoVLM™ video laryngeal mask (VLM) intubation and i-gel combined with flexible bronchoscopy (FB)-guided intubation in airway management during general anesthesia., Methods: A total of 120 adult patients were randomly allocated into the SaCoVLM™ group (Group S) and i-gel group (Group I). After induction of general anesthesia, guided tracheal intubation under direct vision of the SaCoVLM™ was conducted in Group S, while Group I received FB-guided tracheal intubation using the i-gel. The success rate of SAD placement, first-pass success rate of guided tracheal tube placement, and total success rate in both groups were recorded. The time for SAD placement, time for guided tracheal intubation, total intubation time (time for SAD placement and intubation), glottic exposure grading and postoperative intubation complications (i.e., dysphagia, hoarseness, pharyngalgia, etc.) of both groups were also compared., Results: The first-time success rate of SAD placement was 98% in two groups. The first-pass success rate of guided endotracheal intubation was 92% in Group S and 93% in Group I (P = 0.74 > 0.05). The total intubation time was 30.8(± 9.7) s and 57.4(± 16.6) s (95% CI = -31.5 to -21.7) in Group S and Group I, respectively (P < 0.01). The total complication rate was 8% in Group S and 22% in Group I (P < 0.05). The laryngeal inlet could be observed in the S group through the visual system of SaCoVLM™. No dysphagia or hoarseness was reported., Conclusion: SaCoVLM™ can reveal the position of laryngeal inlet, thus providing direct vision for tracheal intubation. SaCoVLM™ -guided intubation is faster, and does not rely on FB, compared to i-gel combined with FB-guided intubation. Besides, SaCoVLM™ has a lower post-intubation complication rate., Trial Registration: Chinese Clinical Trials Registry (ChiCTR2100043443); Date of registration: 18/02/2021., (© 2022. The Author(s).)

The demand for mobile epidemic prevention medical stations originated from the rapid spread of the COVID-19 pandemic. In order to reduce the infection risk of medical practitioners and provide flexible medical facilities in response to the variable needs of the pandemic, this research aimed to design mobile medical stations for COVID-19 epidemic prevention, the emergence of which began in February 2020. The mobile medical stations include a negative pressure isolation ward, a positive pressure swabbing station, a fever clinic and a laboratory. In Taiwan, many medical institutions used the mobile swabbing station design of this study to practice COVID-19 screening pre-tests. Internationally, this study assisted Palau in setting up medical stations to provide anti-epidemic goods and materials. The design of this study not only provides a highly flexible and safe medical environment but the benefits of screening can also be used as resources for medical research, forming an economic circulation for operation sustainability. In addition, the design of this study can also be used during the non-epidemic period as a healthcare station for rural areas or as a long-term community medical station.

Background: This multicenter prospective, randomized controlled clinical trial compared the clinical performance of supraglottic airway device (SAD) BlockBuster TM and laryngeal mask airway (LMA) Supreme for airway maintenance in anesthetized, paralyzed adult patients., Methods: A total of 651 adult patients scheduled for elective surgery in 13 hospitals were randomly allocated into BlockBuster group (n = 351) or Supreme group (n = 300). The primary outcome was oropharyngeal leak pressure (OLP). Duration and ease of insertion, fiberscopic view of positioning, airway manipulations, and complications were also assessed., Results: The OLP was significantly higher in BlockBuster group compared with Supreme group (29.9 ± 4.2 cmH 2 O vs 27.4 ± 4.3 cmH 2 O, p < 0.001). Success rate of insertion at the first attempt (90.2% vs 85.1%, p = 0.027), rate of optimal fiberscopic view (p = 0.002) and satisfactory positioning of SAD (p < 0.001) were significantly increased in BlockBuster group., Conclusions: Both SAD BlockBuster TM and LMA Supreme are safe, effective, and easy-to-use devices for airway maintenance in anesthetized, paralyzed adult patients, but the SAD BlockBuster TM is superior to LMA Supreme in terms of OLP, success rate at the first attempt, and fiber-optic view of positioning., Trial Registration: The trial is registered at www.chictr.org.cn (ChiCTR-ONC-16009105).

Background: Intrauterine adhesionis caused by a variety of reasons, such as damage of the endometrial basal layer, adhesion or occlusion of the uterine cavity or cervix in different degrees. Seriously endangering women's physical and mental health., Objective: The purpose of this paper is to analyze the research development of intrauterine adhesions in recent 15 years, explore the future development direction, and promote the development of this field., Methods: With intrauterine adhesions and Ashman's syndrome as the theme, the related literatures from January 2006 to July 2021 in the Web of Science were searched, and the visual atlas was analyzed by CiteSpace software., Results: A total of 644 literatures were included. The key words related to intrauterine adhesion mainly include adhesion, pregnancy, expression, intrauterine adhesions, women, adhesion molecule, diagnosis, activation, hysteroscopy and fertility, etc. Six clusters were obtained by keywords analysis, involving hysteroscopy, placenta, office hysteroscopy, uterus and laparoscopy. Co-occurrence of keywords shows that the research focus in recent years is on endometrial repair and regeneration., Conclusions: Through the bibliometric analysis of WOS research on intrauterine adhesions in recent 15 years, the comprehensive analysis of countries, institutions, authors and keywords is obtained, which has a clear guiding significance for guiding the future development of intrauterine adhesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Zuo, Zhou and He.)

Accumulated studies have provided controversial evidences of expression patterns and prognostic value of the GATA family in human ovarian cancer. In the present study, we accessed the distinct expression and prognostic roles of 7 individual members of GATA family in ovarian cancer (OC) patients through Oncomine analysis, CCLE analysis, Human Protein Atlas (HPA), Kaplan-Meier plotter (KM plotter) database, cBioPortal and Metascape. Our results indicated that GATA1, GATA3, GATA4 and TRPS1 mRNA and protein expression was significantly higher in OC than normal samples. High expression of GATA1, GATA2, and GATA4 were significantly correlated with better overall survival (OS), while increased GATA3 and GATA6 expression were associated with worse prognosis in OC patients. GATA1, GATA2, GATA3 and GATA6 were closely related to the different pathological histology, pathological grade, clinical stage and TP53 mutation status of OC. The genetic variation and interaction of the GATA family may be closely related to the pathogenesis and prognosis of OC, and the regulatory network composed of GATA family genes and their neighboring genes are mainly involved in Notch signaling pathway, Th1 and Th2 cell differentiation and Hippo signaling pathway. Transcriptional GATA1/2/3/4/6 could be prognostic markers and potential therapeutic target for OC patients., (© 2022. The Author(s).)

Background and Aims: Sec62 is a membrane protein of the endoplasmic reticulum that facilitates protein transport. Its role in cancer is increasingly recognised, but remains largely unknown. We investigated the functional role of Sec62 in gastric cancer (GC) and its underlying mechanism., Methods: Bioinformatics, tissue microarray, immunohistochemistry (IHC), western blotting (WB), quantitative polymerase chain reaction (qPCR), and immunofluorescence were used to examine the expression of target genes. Transwell, scratch healing assays, and xenograft models were used to evaluate cell migration and invasion. Transmission electron microscopy and mRFP-GFP-LC3 double-labeled adenoviruses were used to monitor autophagy. Co-immunoprecipitation (CO-IP) was performed to evaluate the binding activity between the proteins., Results: Sec62 expression was upregulated in GC, and Sec62 upregulation was an independent predictor of poor prognosis. Sec62 overexpression promoted GC cell migration and invasion both in vitro and in vivo. Sec62 promoted migration and invasion by affecting TIMP-1 and MMP2/9 balance. Moreover, Sec62 could activate autophagy by upregulating PERK/ATF4 expression and binding to LC3II with concomitant FIP200/Beclin-1/Atg5 activation. Furthermore, autophagy blockage impaired the promotive effects of Sec62 on GC cell migration and invasion, whereas autophagy activation rescued the inhibitory effect of Sec62 knockdown on GC metastasis. Notably, Sec62 inhibition combined with autophagy blockage exerted a synergetic anti-metastatic effect in vitro and in vivo., Conclusion: Sec62 promotes GC metastasis by activating autophagy and subsequently regulating TIMP-1 and MMP2/9 balance. The activation of autophagy by Sec62 may involve the unfolded protein response (UPR)-related PERK/ATF4 pathway and binding of LC3II during UPR recovery involving FIP200/Beclin-1/Atg5 upregulation. Specifically, the dual inhibition of Sec62 and autophagy may provide a promising therapeutic strategy for GC metastasis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Growing evidence has shown that Transmembrane Serine Protease 2 (TMPRSS2) not only contributes to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but is also closely associated with the incidence and progression of tumours. However, the correlation of coronavirus disease (COVID-19) and cancers, and the prognostic value and molecular function of TMPRSS2 in various cancers have not been fully understood. In this study, the expression, genetic variations, correlated genes, immune infiltration and prognostic value of TMPRSS2 were analysed in many cancers using different bioinformatics platforms. The observed findings revealed that the expression of TMPRSS2 was considerably decreased in many tumour tissues. In the prognostic analysis, the expression of TMPRSS2 was considerably linked with the clinical consequences of the brain, blood, colorectal, breast, ovarian, lung and soft tissue cancer. In protein network analysis, we determined 27 proteins as protein partners of TMPRSS2, which can regulate the progression and prognosis of cancer mediated by TMPRSS2. Besides, a high level of TMPRSS2 was linked with immune cell infiltration in various cancers. Furthermore, according to the pathway analysis of differently expressed genes (DEGs) with TMPRSS2 in lung, breast, ovarian and colorectal cancer, 160 DEGs genes were found and were significantly enriched in respiratory system infection and tumour progression pathways. In conclusion, the findings of this study demonstrate that TMPRSS2 may be an effective biomarker and therapeutic target in various cancers in humans, and may also provide new directions for specific tumour patients to prevent SARS-CoV-2 infection during the COVID-19 outbreak., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: To preliminary evaluate the application of SaCoVLM™ video laryngeal mask airway in airway management of general anesthesia., Methods: We recruited 100 adult patients (ages 18-78 years, male 19, female 81, weight 48-90 kg) with normal predicted airway (Mallampati I ~ II, unrestricted mouth opening, normal head and neck mobility) and ASA I-II who required general anaesthesia. The SaCoVLM™ was inserted after anesthesia induction and connected with the anesthesia machine for ventilation. Our primary outcome was glottic visualization grades. Secondary outcomes included seal pressure, success rate of insertion, intraoperative findings (gastric reflux and contraposition), gastric drainage and 24-h complications after operation., Results: The laryngeal inlet was exposed in all the patients and shown on the video after SaCoVLM™ insertion. The status of glottic visualization was classified: grade 1 in 55 cases, grade 2 in 23 cases, grade 3 in 14 cases and grade 4 in 8 cases. The first-time success rate of SaCoVLM™ insertion was 95% (95% CI = 0.887 to 0.984), and the total success rate was 96% (95% CI = 0.901 to 0.989). The sealing pressure of SaCoVLM™ was 34.1 ± 6.2 cmH 2 O and the gastric drainage were smooth. Only a small number of patients developed mild complications after SaCoVLM™ was removed (such as blood stains on SaCoVLM™ and sore throat)., Conclusions: The SaCoVLM™ can visualize partial or whole laryngeal inlets during the surgery, with a high success rate, a high sealing pressure and smooth gastroesophageal drainage. SaCoVLM™ could be a promise new effective supraglottic device to airway management during general anesthesia., Trial Registration: ChiCTR, ChiCTR2000028802 .Registered 4 January 2020., (© 2021. The Author(s).)

Objective: The present study aims to explore the effectiveness and safety of low-dose strong opioids compared with non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of mild cancer pain., Methods: From September 2016 to September 2018, 66 patients with a malignant tumor and mild cancer pain admitted to the Department of Oncology of Dalian Fifth People's Hospital were divided into the group A (treated with ibuprofen sustained-release tablets for pain relief) and the group B (treated with oxycodone hydrochloride sustained-release tablets for pain relief). After 7 days of treatment, the pain relief (Numeric Rating Scale [NRS]), physical strength, quality of life scores (Zubrod/ECOG/WHO [ZPS]), the Edmonton Symptom Assessment System [ESAS], and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core15-Palliative [EORTC QLQ-C15-PAL] scores), and the occurrence of adverse reactions between the two groups were compared. The occurrence of adverse reactions in the mid-term (after one month and three months of treatment) between the two groups were also compared., Results: Both groups had over 90% analgesic efficiency, but complete pain relief was more likely to be obtained in the group B (41.18%). The total analgesic efficiency in the group B was higher (100%) than in the group A (98.9%), and the difference was statistically significant (P < 0.05). The differences in the physical strength and quality of life scores in the two groups before and after treatment were statistically significant (P < 0.05). The differences in the ZPS scores between the two groups were statistically significant (P < 0.05). The differences in ESAS and EORTC QLQ-C15-PAL scores between groups were not statistically significant (P > 0.05)., Conclusion: The application of low-dose oxycodone hydrochloride sustained-release tablets as the initial medication for patients with mild cancer pain was safe and effective, and the adverse reactions were easy to manage., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Background: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients., Methods: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival., Results: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815., Conclusions: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Background: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery., Methods: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days., Results: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001)., Conclusions: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Gynecologic cancer is a serious global healthcare issue with high rates of mortality and morbidity. In recent years, tumor immunity and immunotherapy have attracted extensive attention for treatment of gynecological cancers. Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a critical role in cancer immune escape, and its inhibition has been explored for immune-targeted therapies for many malignancies. However, knowledge about IDO1 involvement in the pathogenesis of gynecological cancers and its therapeutic potential is still evolving. In the current study, we integrated bioinformatics analysis of the prognostic value and immune function of IDO1 in gynecologic malignancies using Oncomine, GEPIA, HPA, TIMER, TISIDB, SurvExpress and Metascape database. Comprehensive analysis revealed that the transcription levels of IDO1 were significantly overexpressed in patients with gynecologic cancers, and IDO1-co-expressed gene signatures may be useful potential prognostic markers for gynecologic cancers. Furthermore, increased IDO1 expression correlated with immune infiltration cells, immune marker sets, and immunomodulators in gynecological cancers. These findings suggest that IDO1 plays an important role in immune infiltration and could potentially be an immunotherapeutic target for gynecological cancers. However, future large-scale and comprehensive research is required to validate our results., Competing Interests: None., (AJTR Copyright © 2021.)

Objectives: Postoperative acute kidney injury (AKI) has an unfavorable impact on both short-term and long-term outcomes. The aim of this retrospective study was to compare the incidence of postoperative AKI between laparoscopic and laparotomy procedures in elderly patients undergoing colorectal surgery., Methods: Medical records of elderly (65 y and older) patients who underwent colorectal cancer surgery between May 2016 and July 2018 at our tertiary hospital were reviewed. Patients with Union Internationale Contre le Cancer (UICC) stage II and III colorectal cancer, without neoadjuvant treatment, were divided into laparoscopic procedure group and laparotomy group. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups, before and after propensity matching. Multivariable analysis was made to identify independent risk factors of AKI., Results: In all, 285 patients met the study inclusion criteria. Postoperative AKI occurred only in 16 patients from the laparotomy group (n=212). The incidence of AKI was significantly lower in the laparoscopic procedure group (n=73) compared with the laparotomy group (0% vs. 7.5%; P=0.015). Seventy-three patients who underwent laparoscopic surgery were matched with 73 of 212 patients who underwent open surgery, by using propensity score analysis, and the incidence of AKI in the 2 groups was similar (0% vs. 8.3%; P=0.028). Multivariable analysis showed that intraoperative metaraminol dose >1 mg (odds ratio=2.742, P=0.042) is an independent risk factor for postoperative AKI., Conclusion: In elderly patients, the incidence of AKI after colorectal cancer surgery is lower in the laparoscopic procedure group, maybe related to hemodynamic stability and less vasoconstriction., Competing Interests: The author declares no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma (PBL) is a rare entity of diffuse large B-cell lymphoma (DLBCL). The clinicopathological features of and optimal treatment for HIV-negative PBL remain largely unknown., Methods: To gain insight into this distinct lymphoma, we summarized the clinicopathologic characteristics of 8 unpublished HIV-negative PBLs and performed a comprehensive review of 394 published cases., Results: Of the 8 unpublished PBLs, the median patient age was 53.0 years. Four patients presented with stage IV disease. All 8 patients showed a plasma cell-like immunophenotype. Of the six patients who received anthracycline-based chemotherapy, including two who received bortezomib, three patients achieved a continuous complete response, two patients died due to disease progression, and one patient was lost to follow-up. The other two patients achieved continuous complete response after receiving chemotherapy combined with radiotherapy and surgery. Of the 402 patients, the majority were male, with a mean age of 58.0 years. EBV infection was detected in 55.7% of the patients. The median survival times of the patients who received CHOP or CHOP-like regimens and intensive regimens were not reached and 23.0 months, respectively, and the intensive regimen did not improve the survival outcome ( P =0.981). Multivariate analysis showed that EBER remained the only independent factor affecting overall survival (OS)., Conclusion: HIV-negative PBL is a distinct entity with a predilection for elderly and immunosuppressed individuals. Intensive chemotherapy had no apparent survival benefits over the CHOP regimen in terms of OS; the prognosis of this disease is poor with current chemotherapy methods, and treatment remains a challenge., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported., (© 2020 Korean Society of Hematology.)

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

Aims: Non-small cell lung cancer (NSCLC), characterized by extensive metastasis and poor prognosis, is the most common type of lung cancer. Dysregulation of certain lncRNAs is known to be linked to the tumorigenesis of NSCLC. However, the specific roles in NSCLC for many other lncRNAs, such as linc01088, remain largely unknown., Materials and Methods: The expression patterns of linc01088, p21 and EZH2 were examined both in NSCLC tissues and cell lines using RT-qPCR assay. CCK-8, colony formation, immunofluorescence staining, and flow cytometry assays were employed to evaluate the effects of linc01088 on NSCLC cell proliferation properties. RNA immunoprecipitation (RIP) assay was performed to determine the direct binding relationship between linc01088 and zeste homolog 2 (EZH2). Western blot and RT-qPCR analysis were performed to assess p21 level within knockdown of either linc01088 or EZH2. Nude mouse subcutaneous NSCLC models were constructed for further validating the effects and mechanisms of linc01088 in vivo., Key Findings: linc01088 and EZH2 were highly expressed both in NSCLC tissues and cell lines. Knockdown of linc01088 suppressed the proliferation of NSCLC cells, and prolonged the G1 phase while shortened S and G2-M phases. RIP assay revealed the direct binding relationship between linc01088 and EZH2. Knockdown of either linc01088 or EZH2 induced up-regulation of p21 expression, which subsequently inhibited the tumor growth., Significance: We demonstrated that linc01088 could promote cell proliferation via binding with EZH2 to repress p21, which aggravates the tumorigenesis of NSCLC. Therefore, linc01088 might be a potential oncogene and target for novel anti-tumor therapies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cathepsin L (CTSL) is a lysosomal acid cysteine protease that has been implicated in tumorigenesis and malignant progression. In the present study, the role of CTSL in tumorigenesis and prognosis of breast cancer was evaluated. The prognostic value of CTSL was analyzed using immunohistochemistry in patients with breast cancer, as well as online microarray datasets. CTSL expression was knocked down in the breast cancer cell line T-47D using RNA interference. MTT and colony formation assays were performed to assess the role of CTSL in the proliferation of breast cancer cells. Cell cycle progression and apoptosis were measured using flow cytometry. A physical interaction of CTSL and cyclin dependent kinase 2 associated protein 1 (CDK2-AP1) was determined using a glutathione S-transferase pull-down assay. Endogenous CTSL expression was high in breast cancer cells and exhibited an inverse association with CDK2-AP1 expression; aberrant expression of CTSL in breast cancer tissues predicted an improved clinical outcome and prognosis. In addition, CTSL knockdown decelerated the progression of breast cancer cells by arresting cell cycle progression and increasing apoptosis. Thus, CTSL may be a potential therapeutic target for treating patients with breast cancer., (Copyright: © Wang et al.)

Background: In recent years, with the popularity of laryngeal mask airway (LMA) for the management of clinical anesthesia, the influence of the LMA on the position and blood flow of the internal jugular vein (IJV) has attracted an increasing amount of attention., Aim: To investigate the effect of placement of different types of LMA (Supreme LMA, Guardian LMA, I-gel LMA) on the position and blood flow of the right IJV., Methods: This was a prospective randomized controlled trial. A total of 102 patients aged 18-75 years who were scheduled to undergo laparoscopic abdominal surgery with general anesthesia were randomly assigned to three groups: Supreme LMA (group 1), Guardian LMA (group 2), and I-gel LMA (group 3) groups. The main indicator was the overlap index (OI) of IJV and the common carotid artery (CCA) at the high, middle, and low points before and after the placement of the LMA. The second indicators were the proportion of ultrasound-simulated needle crossing the IJV and CCA, and the cross-sectional area and blood flow velocity of the IJV before and after placement of the LMA at the middle point., Results: Data from 100 patients were included in the statistical analysis. The OI increased significantly after placement of the LMA in the three groups at the three points ( P < 0.01), except group 2 at the low point. In group 2 and group 3, the OI was lower than that in group 1 after LMA insertion at the high point ( P < 0.0167). At the middle point, after LMA insertion, the proportion of simulated needle crossing the IJV significantly decreased in all three groups ( P < 0.05), and the proportion in group 2 was higher than that in group 3 ( P < 0.0167). The proportion of simulated needle crossing the CCA or both the IJV and CCA significantly increased in group 1 and group 2 ( P < 0.05), which increased with no statistical significance in group 3. After LMA insertion, the cross-sectional area of ​​the IJV significantly increased, while the blood flow velocity significantly decreased ( P < 0.01). There was no significant difference among the three groups., Conclusion: The placement of Supreme, Guardian, and I-gel LMA can increase the OI, reduce the success rate of IJV puncture, increase the incidence of arterial puncture, and cause congestion of IJV. Type of LMA did not influence the difficulty of IJV puncture. Therefore when LMA is used, ultrasound is recommended to guide the IJV puncture., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we investigated the distinct expression and prognostic value of E2Fs in patients with OC by analyzing a series of databases, including ONCOMINE, GEPIA, cBioPortal, Metascape, and Kaplan-Meier plotter. The mRNA expression levels of E2F1/3/5/8 were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC. Aberrant expression of E2F2/5/7/8 was found to be associated with the clinical outcomes of patients with OC. These results suggest that E2F2/5/8 might serve as potential prognostic biomarkers and targets for OC. However, future studies are required to validate our findings and promote the clinical utility of E2Fs in OC.

YES is a member of the SRC family kinase (SFK) group of non-receptor tyrosine kinases, which are implicated in multiple key cellular processes involved in oncogenesis. Antitubulin agents have been widely used as chemotherapeutics for cancer patients and these drugs arrest cells in mitosis, leading to subsequent cell death. In the present study, we define a mechanism for phospho-regulation of YES that is critical for its role in response to antitubulin agents. Specifically, we found that YES is phosphorylated at multiple sites on its N-terminal unique domain by the cell cycle kinase CDK1 during antitubulin drug-induced mitotic arrest. Phosphorylation of YES occurs during normal mitosis. Deletion of YES causes arrest in prometaphase and polyploidy in a p53-independent manner. We further show that YES regulates antitubulin chemosensitivity. Importantly, mitotic phosphorylation is essential for these effects. In support of our findings, we found that YES expression is high in recurrent ovarian cancer patients. Finally, through expression profiling, we documented that YES phosphorylation affects expression of multiple cell cycle regulators. Collectively, our results reveal a previously unrecognized mechanism for controlling the activity of YES during antitubulin chemotherapeutic treatment and suggest YES as a potential target for the treatment of antitubulin-resistant cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The development of sensitive myocardial-specific cardiac biomarkers allows for detection of very small amounts of myocardial injury or necrosis. Myocardial injury (MI) as a prelude of the serious perioperative complication myocardial infarction, should be paid more attention, especially in elderly susceptible patients. Myocardial injury after abdominal surgery in elderly patients has not been described yet. The objectives of this study were to identify the incidence, predictors, characteristics and the impact of MI on outcome in elderly patients underwent abdominal surgery., Methods: Patients aged  ≥ 65 who underwent abdominal surgery longer than 2 h between January 2016 and March 2017 were reviewed. Patients with peak troponin I level of 0.04 ng/ml or greater (abnormal laboratory threshold) within once-administration-period and without non-ischemia troponin elevation proof (e.g., sepsis) were assessed for characteristics and prognosis. Risk factors of MI were determined by multivariable regression., Results: Among 285 patients with whole information, 36 patients (12.6%) suffered MI, only 2 patients (0.7%) fulfilled definition of myocardial infarction. With most of them occurred within first 7 days after surgery. Multivariable analysis showed that coronary artery disease (CAD) history [odds ratio (OR) 2.817, P = 0.015], non-laparoscopic surgery (OR 5.181, P = 0.030), blood loss ≥ 800 ml (OR 3.430, P = 0.008), non-venous maintain (OR 2.105, P = 0.047), and infection (OR 4.887, P = 0.008) as risk factors for MI. MI was associated with longer hospital stay (P = 0.006), more cardiac consultation (P = 0.011), higher infection(P = 0.016) and reoperation(P = 0.026) rate., Conclusion: MI is common in elderly patients who underwent abdominal surgery, while myocardial infarction is infrequent. They are both associated with risk factors and worse prognosis. MI deserves more attention especially in elderly patients. Troponin I measurement is a useful test after massive surgery, which can help risk-stratifying patients, effective preventing, prompt managing and predicting outcomes. Routine monitoring of cardiac biomarkers especially within 7 days after abdominal surgery in elderly patients is recommended.

Background: Pelvic organ prolapse (POP) seriously affects the life quality of old females. In the present work, we described the knowledge structure of POP in a macroscopic view, and summarized the recent research focus., Methods: Candidates were identified through reading and screening publications from PubMed database with a MeSH term of "pelvic organ prolapse" during 2007-2016. Relevant journals and journal-affiliated countries were extracted, and essential information, such as the number of publication of each year, first authors and MeSH/subheading words, was analyzed with BICOMB. In addition, highly-frequent MeSH/subheading words were determined and classified, and co-occurrence matrices were produced accordingly. Finally, social network was utilized to analyze the knowledge structure., Results: A total of 3294 publications of POP were retrieved from 364 journals. The publication of POP had a significant downward trend since the beginning of 2015. POP articles published in American and British journals were significantly more compared with other countries. The co-occurrence matrices of 37 × 37 and 55 × 55 were produced by the highly-frequent MeSH/subheading words, and then the social network analysis was performed based on them., Conclusion: These publications on POP were mainly from the developed countries. Surgical treatment of POP was a hot topic of POP research in recent 10 years., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: Circulating microRNAs (miRNAs) are proposed as promising non-invasive diagnostic biomarkers for many cancers. However, the diagnostic value of circulating miRNAs in ovarian cancer is inconsistent in different studies. Thus we performed this meta-analysis to systematically evaluate the diagnostic value of circulating miRNAs in ovarian cancer., Methods: Eligible studies that were published prior to 30 June 2017 were searched from the PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure. All analyses were performed using STATA 12.0 software. A bivariate regression was used to calculate pooled diagnostic accuracy estimates., Results: A total of 36 studies from 16 publications were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for ovarian cancer diagnosis were 0.76 (95% confidence intervals (CI): 0.69, 0.81), 0.81 (95% CI 0.74, 0.87), 4.00 (95% CI 2.70, 5.30), 0.30(95% CI 0.24, 0.37) and 13.00 (95% CI 9.00, 19.00), respectively. The area under the summary receiver operating characteristic curve was 0.85 (95% CI 0.82, 0.88). Subgroup analyses showed that multiple miRNA assays yielded better diagnostic characteristics than a single miRNA assay, and plasma miRNAs were better than serum miRNAs for ovarian cancer detection., Conclusion: Circulating miRNAs, especially the combination of multiple circulating miRNAs, are promising biomarkers for the diagnosis of ovarian cancer. However, further large-scale prospective studies are necessary to validate the applicability of the miRNAs in the early detection of ovarian cancer.

Objectives: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients with ENKTCL., Methods: Newly diagnosed ENKTCL patients treated with either the GELOXD or the P-GEMOXD regimen were identified from three cancer centers between January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were used to calculate overall survival (OS) and progression-free survival (PFS) and to investigate prognostic factors., Results: One hundred and eighty-four cases were identified from three cancer centers. After 1-5 treatment cycles of GELOXD or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The 3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates were significantly higher in early-stage patients compared with advanced-stage patients. A multivariate analysis revealed that patient CR status was a significant independent factor in disease prognosis. Grade 3/4 leukopenia occurred in 43 (23.4%) patients. Major non-hematological toxicities included nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%)., Conclusions: The GELOXD and P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival outcomes in patients with ENKTCL., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previously we showed that aldehyde dehydrogenase 1A1 (ALDH1A1) is a new mediator for resistance of DLBCL to CHOP and a facility predictor of clinical prognosis. In the present study, knockdown and inhibitor of ALDH1A1 were applied to identify the role of ALDH1A1 in Raji cells. CCK-8 and clone formation assay were applied to determine the CHOP sensitivity and clone formation ability. Caspase colorimetric assay and Annexin V/FITC staining was performed to determine the degree of apoptosis. Western blot analysis was used to detect the NF-κB/STAT3 signaling proteins and apoptotic-associated proteins. Real-time quantitative PCR (RT-PCR) was used to identify the differential expression of ALDH1A1 between NHL patients and healthy donors. We demonstrated that inhibition of ALDH1A1 increased the sensitivity of Raji cells to CHOP, as indicated by increased cytotoxicity, reduced clonogenicity, activated caspase-3/-9, decreased NF-κB/STAT3 signaling and increased pro-apoptosis signaling, ad increased apoptosis rate. Moreover, we found high ALDH1A1 expression was associated with poor prognosis in NHL patients. Our data revealed the critical role of ALDH1A1 in NHL and provides a theoretical basis for the use of ALDH1A1 inhibitors in NHL patients.

The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.

Aim: Increasing evidence indicates that platelet count is a useful biomarker of long-term outcomes in patients with ovarian cancer. However, the prognostic value of platelet count in patients with ovarian cancer remains controversial. We therefore conducted a meta-analysis aimed to investigate the prognostic role of the platelet count in patients with ovarian cancer., Method: A comprehensive search was performed from the databases of PubMed, Embase and the Cochrane Library until June 20, 2017. A total of 18 studies with 6754 patients were included. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) and odds ratios and 95% CIs from each study were pooled., Results: The results demonstrated that elevated pretreatment platelet count was significantly related to poor survival from ovarian cancer; the pooled HRs for overall, progression-free and disease-free survival were 1.81 (95% CI 1.52-2.15), 1.48 (95% CI 1.24-1.75) and 1.39 (95% CI 1.19-1.61), respectively. Subgroup analyses were divided by ethnicity, sample size, FIGO stage, cut-off value of the platelet count, analysis method and Newcastle Ottawa Scale score, but the results did not show any significant change in the main results. Increased platelet count was also significantly associated with the FIGO stage, tumor differentiation, ascites, residual tumor mass, CA125 level, recurrence and metastasis., Conclusion: This meta-analysis revealed that an elevated platelet count pretreatment denotes a predictive factor of poor prognosis and unfavorable clinicopathological parameters for ovarian cancer patients.

Objective: To explore the relationship between gasdermin D (GSDMD) and gastric cancer (GC) cell proliferation, and to determine whether the downregulated expression of GSDMD contributed to the tumorigenesis and proliferation of GC cells., Methods: GSDMD expressions in GC tissues and matched adjacent non-cancerous tissues were assessed by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. The effect of GSDMD on cell proliferation in vitro was assessed by the colony formation assay and cell viability assays. In vivo, xenografted tumors in nude mice were evaluated. The cell cycle was analyzed by flow cytometry. In addition, the alterations of several cell cycle-related and cell signaling pathway proteins were analyzed by Western blot., Results: GSDMD expression was decreased in GC, and the decreased expression of GSDMD could markedly promote the proliferation of tumors in vivo and in vitro. The downregulation of GSDMD accelerated S/G 2 cell transition by activating extracellular signal regulated kinase, signal transducer and activator of transcription 3 and phosphatidylinositol 3 kinase/protein kinase B signaling pathways and regulating cell cycle-related proteins in GC., Conclusion: GSDMD may protect against cell proliferation of GC, and it may be used as a diagnostic and treatment strategy for GC., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Nucleic acid oxidation plays an important role in the pathophysiology progress of a variety of diseases. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), which originate from DNA and RNA oxidation, were the most widely used indicators for oxidative stress. The study investigated the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD. 146 patients with CKD were divided into five disease stages, and their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by LC-MS/MS. The ratio of urinary 8-oxo-Gsn to creatinine increased from stages 1 to 4 corresponding to the increased severity of CKD, but it decreased in stage 5. And plasma 8-oxo-Gsn gradually increased with the decline of renal function. In particular, the increased ratio of plasma and urine 8-oxo-Gsn in stage 5 exceeded the concentration of creatinine. This trend was similar to the estimated glomerular filtration rate (eGFR), which indicates that 8-oxo-Gsn could be an appropriate indicator for renal function. Our finding indicates that as the disease progresses, RNA oxidation is increased. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is a novel evaluation index of end-stage renal disease.

One of the important features of inflammatory bowel disease (IBD) is dysbiosis of the gut microbiota. It has been well documented that changes in the commensal bacterial population are involved in IBD development. However, the function of the fungal and viral communities in IBD remains unclear. Moreover, the optimal treatment for IBD patients with opportunistic infections is still undecided. This review focused on how the enteric mycobiota and virome changes during the pathogenesis of IBD and discussed potential treatment strategies that open new insights into the managements of IBD., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To investigate the preliminary applicability of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score in the condition of 3.0T multi-parametric magnetic resonance imaging (Mp-MRI) combined with clinical classic indicators for the diagnosis of prostate cancer (PCa). Methods: The clinical and MRI materials of 247 patients of suspicious prostate disease treated in Second Affiliated Hospital of Soochow University from June 2015 to November 2016 were analyzed retrospectively, including 110 cases with PCa and 137 cases without cancer.All cases underwent the high-resolution axial T(2)-weighted imaging (T(2)WI), diffusion weighted imaging (DWI) and dynamic contrast enhancement-magnetic resonance imaging (DCE-MRI) and were confirmed pathologically by puncture biopsies.The Mp-MRI materials of all cases were scored according to PI-RADS v2.The prostate volume and prostate specific antigen (PSA) density (PSAD) value were calculated according to the formulas.The univariate and multivariate analysis were performed for the observed indicators (age, prostate volume, PSA, PSAD and PI-RADS v2 score) to determine the independent predictors for PCa.Then, a Logistic regression model (combined prediction model) was established by the independent predictors for combined diagnosis of PCa.The receiver operating characteristic curve (ROC) curve analysis was performed to get the sensitivity and specificity of each independent predictor and the model to diagnose PCa.The differences of AUC values of each independent predictor and the model were compared with each other to evaluate the diagnostic performance for PCa. Results: The differences in the age, prostate volume, PSA, PSAD and the PI-RADS v2 score between patients with PCa and non-cancer group were all statistically significant ( t =2.870, Z =-4.230, -7.787, -9.477, -10.826, all P <0.05). The PSAD and PI-RADS v2 score were independent predictors for PCa ( OR =3.331, 10.546, both P <0.05). The Logistic regression combined prediction model by PI-RADS v2 score and PSAD to forecast PCa was Logit( P )=-5.097+ 2.309×PSAD+ 1.214×PI-RADS v2 score.The area under the curve (AUC) of ROC in the combined model (0.911) was higher than that in the PI-RADS v2 score (0.886) and PSAD (0.851) and the differences were all statistically significant ( Z =2.416, 2.716, both P <0.05); but the difference in the AUC value between PI-RADS v2 score and PSAD was not statistically significant ( Z =1.191, P =0.234). The diagnostic sensitivity of PSAD, PI-RADS v2 score and the model were: 0.891, 0.782 and 0.855, respectively; the specificity were 0.449, 0.912 and 0.847, respectively on their positive thresholds (0.15 μg·L(-1)·ml(-1,) 4 and -0.82). Conclusion: PI-RADS v2 score combined with PSAD in diagnosing PCa is superior to the single application of them and it can lead to high diagnostic sensitivity and specificity for PCa.

Increasing evidence indicates that elevated neutrophil to lymphocyte ratio (NLR) are related with poor prognosis in various types of tumors. However, the prognostic role of NLR in patients with ovarian cancer (OC) remains controversial. Thus, the current meta-analysis aimed to investigate the prognostic role of NLR in patients with OC. A total of 16 studies with 4,910 patients were included. By pooling hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs from each study. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR: 1.50, 95% CI: 1.27-1.77) and PFS (HR: 1.53, 95% CI: 1.28-1.84) in patients with OC. Subgroup analyses was divided by ethnicity, sample size, histologic types, cut-off value of NLR, analysis method and NOS score, but the results did not showed any significant change the main results. This meta-analysis revealed that elevated pretreatment NLR might be a predicative factor of poor prognosis in OC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Platelet-derived growth factor receptor (PDGFR)-β is an important tyrosine kinase and its downregulation has been reported to alter the radiosensitivity of glioma cells, although the underlying mechanism is unclear. In order to investigate the effect of PDGFR-β on the radiosensitivity of glioblastoma, the present study transfected C6 glioma cells with a PDGFR-β-specific small interfering (si)RNA expression plasmid, and downregulation of the expression of PDGFR-β in C6 glioma cells was confirmed by western blotting and immunohistochemical analysis. Clone formation assays and xenograft growth curves demonstrated that PDGFR-β-siRNA enhanced the radiosensitivity of C6 glioma cells in vitro and in vivo . Furthermore, MTT and xenograft growth curves demonstrated that PDGFR-β-siRNA inhibited the proliferation of C6 glioma cells in vitro and in vivo , and terminal deoxynucleotidyl transferase dUTP nick end-labeling and immunohistochemical analyses demonstrated that PDGFR-β-siRNA induced apoptosis and inhibited the expression of Ki-67, cyclin B1 and vascular endothelial growth factor in C6 glioma cell xenografts. Taken together, these results suggested that PDGFR-β may be used as a target for the radiosensitization of glioblastoma.

Oxidatively generated damage to nucleic acids may play an important role in the pathophysiological processes of a variety of diseases. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) are oxidatively generated products of DNA and RNA, respectively. Our previous studies have suggested that the amounts of 8-oxo-dGsn and 8-oxo-Gsn in urine were considerably higher than other body fluid or tissue. The aim of this study was to investigate whether 8-oxo-dGsn and 8-oxo-Gsn levels in random urine samples are consistent with those in 24 h urine samples in healthy subjects and patients with renal disease. A total of 16 healthy subjects and 104 renal disease patients were enrolled in this study, and their random and 24 h urine samples were collected. The levels of urinary 8-oxo-dGsn and 8-oxo-Gsn were quantified by LC-MS/MS and corrected by creatinine. Regardless of healthy subjects or renal disease patients, the levels of oxidised nucleosides in random urine samples were consistent with 24 h urine samples. Regardless of the age bracket, there is no significant difference between random samples and 24 h urine samples. In conclusion, 8-oxo-dGsn and 8-oxo-Gsn levels in random urine samples could replace those in 24 h urine samples, and were considered as the representative of the level of systemic oxidative stress for the whole day.

We investigated the effects of tumor suppressor candidate 3 ( TUSC3 ) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

The present study aims to explore the relationship between the Y chromosome polymorphisms (1qh+, inv(9), 9qh+, 16qh+, group D/G, Yqh- and Yqh+) and the risk of unexplained recurrent miscarriage (URM). A total of 507 couples with URM were recruited as case group and 465 healthy couples as control group. The Y chromosome polymorphisms of the male individuals were analysed with the G-banding technique, and the results of the chromosome G-banding analysis were determined using the International Naming Standards of Human Genetics (ISCN). Logistic regression analysis was used to analyse the risk factors for URM. The detection rate of Y chromosome polymorphisms in the case group (12.03%) was higher than that in the control group (2.15%). Y chromosome polymorphisms were detected at significantly higher rates in the case group than in the control group. Using the normal Y chromosomes in individuals of the case group as reference, the partners of their counterparts were more likely to experience miscarriage. The couples who were Y chromosome-polymorphism carriers had shorter gestational age, increased frequency of URM and longer average interval between pregnancies. The results of logistic regression analysis revealed that Y chromosome polymorphisms, shorter gestational age, a higher frequency of miscarriage and longer pregnancy interval were independent risk factors for URM. Y chromosome polymorphisms may be associated with the risk of URM and may play an important role in the development of URM., (© 2017 The Author(s).)

Purpose: To investigate the associations of ANLN expression with prognosis of breast cancer and clinical outcome of anthracycline-based chemotherapy., Methods: This study enrolled 308 breast cancer patients in which 264 of them received anthracycline-based chemotherapy. Immunohistochemistry was used to detect ANLN expression level of the patients. Clinical characteristics of the patients were collected, and associations of ANLN expression with prognosis were analyzed., Results: Our results showed that ANLN expression was associated with survival of breast cancer patients, and it was also related to clinical outcome of patients received anthracycline-based chemotherapy. Breast cancer patients with high expression of ANLN would have poor prognosis and poor clinical outcome to anthracycline-based chemotherapy., Conclusion: ANLN could be an independent prognosis predictor for breast cancer, and its expression might be used to predict the anthracycline-based chemotherapy clinical outcome in breast cancer patients.