Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Nephrotoxicity of immune checkpoint inhibitor combination therapy in patients with advanced renal cell carcinoma: a meta-analysis.

PURPOSE: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. METHODS: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. RESULTS: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77-1.37, P = 0.87) and grade 3-5 (RR = 1.48, 95% CI: 0.19-11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54-3.51, P < 0.0001) and grade 3-5 proteinuria (RR = 2.25, 95% CI: 1.21-4.17, P = 0.01). CONCLUSIONS: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic.

Symptom management in adult brain tumours: A literature review.

AIM: To review the literature related to symptom management, clinical significance and related theoretical framework systems in adult patients with brain tumours. BACKGROUND: As understanding of symptoms or symptom clusters and underlying biologic mechanisms has grown, it is apparent that symptom science is moving forward. Although some progress has been made in the symptom science of solid tumours such as breast and lung neoplasms, insufficient attention has been paid to symptom management for patients suffering from brain tumours. Further research is needed to achieve effective symptom management for these patients. DESIGN: A literature review with a systematic search of symptom management in adult brain tumours. METHODS: Electronic data bases were searched to obtain relevant published literature on symptom management in adults with brain tumours. This was then analysed and a synthesis of relevant findings is presented. FINDINGS: Four significant general themes relating to symptom management of brain tumours in adults were identified: (1) The potential theoretical foundation related to symptom management was revealed. (2) Widely accepted validated scales or questionnaires for the assessment of single symptoms or symptom clusters were recommended. (3) Several symptom clusters and the underlying biologic mechanisms have been reported. (4) Specific symptom interventions for adults with brain tumours were collected and classified as evidence-based or insufficient evidence. CONCLUSION: There are still many challenges in the effective management of symptoms in adults with brain tumours. The guiding role of theoretical frameworks or models related to symptom management should be utilized in future research. Using the concept of symptom clustering for research into symptoms found in patients with brain tumours, exploring common biological mechanisms for specific symptom clusters and making full use of modern big data resources to build a strong evidence base for an effective intervention or management program may inform the management of symptoms among these patients leading to better results. NO PATIENT OR PUBLIC CONTRIBUTION: This is a literature review. IMPLICATIONS FOR SYMPTOM MANAGEMENT: The ultimate goal is obviously not only improving the survival rate of patients with brain tumours, but also enhancing their quality of life. Several important findings from our review include the theoretical foundations, validated assessment tools, the assessment of symptom clusters and the underlying biologic mechanism, and the identification of the evidence base for symptom interventions. These are of relevance for managers, researchers and practitioners and may function as a reference to help the effective symptom management for adults with brain tumours.

Smoking affects the association between cognitive impairment and P50 inhibition defects in patients with chronic schizophrenia: A case-control study.

OBJECTIVE: Smoking affects sensory gating, as assessed by the event related potential P50, which is evoked by auditory stimuli and is considered to be involved in the pathophysiology of schizophrenia (SCZ). However, few studies have compared sensory gating and cognitive performance between smoking and non-smoking SCZ patients in the Chinese Han population. METHODS: We recruited two groups of Chinese subjects: 128 male chronic SCZ patients and 76 male healthy controls, measuring cognition with the MATRICS Consensus Cognitive Battery (MCCB) and sensory gating with the P50 EEG components. Based on their smoking status, they were further divided into 4 subgroups: smoking SCZ patients, non-smoking SCZ patients, smoking healthy controls, and non-smoking healthy controls. We assessed psychopathological symptoms of the patients using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, SCZ patients had lower MCCB total score and scores of all 10 tests (all p < 0.05), while SCZ patients had higher S2 amplitudes and P50 ratios (both p < 0.05). When comparing smoking versus non-smoking SCZ patients, non-smokers had significantly better spatial span (p < 0.05). Furthermore, the S1 amplitude was negatively correlated with the Brief Visuospatial Memory Test (BVMT-R) in smoking patients (p < 0.05), while the S1 latency was negatively correlated with spatial span in non-smoking patients (p < 0.01). CONCLUSIONS: Our finding shows a difference in the relationship between sensory gated P50 and cognition in smoking and non-smoking SCZ patients, suggesting that nicotine may improve cognitive and P50 deficits in SCZ patients.

Integrity of the editing and publishing process is the basis for improving an academic journal's Impact Factor.

BACKGROUND: Journal Impact Factor™ (JIF) is often used to evaluate the relative reputation and quality of academic journals in their respective fields, and can greatly influence the quality and scope of subsequent manuscript submissions. Therefore, many if not all academic journals are interested in increasing their JIF, to improve their academic impact. AIM: To determine the importance of the integrity of the editorial and publication process in improving the academic influence of academic journals and the JIF of academic journals. METHODS: In this paper, we describe our statistical analysis of bibliometric factors - including the 2021 JIFs released in the Journal Citation Report™ 2022, discipline rankings, received and published articles in 2019-2021, and webpage visits and downloads - for seven journals published by Baishideng Publishing Group (Baishideng) and indexed in Science Citation Index Expanded™; ultimately, we introduce and discuss the editing and publishing processes of Baishideng's journals in their entirety, as they form the basis for our objective of safeguarding and bolstering integrity in academic publication. RESULTS: For the seven journals assessed, their 2021 JIFs were basically unchanged from 2020, with the current metric ranging from 5.374 for World Journal of Gastroenterology (WJG) to 1.534 for World Journal of Clinical Cases (WJCC). Further assessments of the journals' bibliometrics from 2019 to 2020, showed that World Journal of Stem Cells has the highest self-citation rate (1.43%) and World Journal of Gastrointestinal Surgery has the lowest (0.21%). Additionally, the total 3012 articles published during this period were cited by more than 20000 articles in approximately 8000 academic journals. Of note, the 1102 articles published in WJG were cited by articles in 3059 journals, among which 171 journals have a JIF of > 10, including internationally renowned academic journals such as CA-A Cancer Journal for Clinicians (2021 JIF 286.130, record count: 1), Lancet (2021 JIF 202.731, record count: 4), Nature Reviews Immunology (2021 JIF 108.555, record count: 2), Nature Reviews Gastroenterology & Hepatology (2021 JIF 73.082, record count: 9), Lancet Gastroenterology & Hepatology (2021 JIF 45.042, record count: 8), Gastroenterology (2021 JIF 33.883, record count: 19), and Gut (2021 JIF 31.793, record count: 21). This suggests that Baishideng's journals have been widely recognized for their academic quality. In the Reference Citation Analysis (RCA) database, all seven Baishideng-published journals obtained a 2022 Journal Article Influence Index (JAII). For example, WJG has a 2022 JAII of 22.048, ranking 18th out of 102 journals in the field of gastroenterology & hepatology in the RCA, with 469909 total citations (6/102) and 21313 total articles (5/102). The numbers of manuscripts received and published in 2021 were both higher than those in 2019-2020. For example, WJCC received a total of 3650 manuscripts in 2021, which is 91.1% higher than those in 2019-2020 (average: 1910 papers/year). In 2021, WJCC published 1296 articles, representing an increase of 105.1% compared to those in 2019-2020 (average: 632 articles/year). The numbers of webpage visits and downloads received by the seven journals have increased year by year. For example, the number of total visits received by WJG in 2019-2021 was 1974052 in 2019, 2317835 in 2020 (increased by 17.4% compared with that in 2019), and 2652555 in 2021 (increased by 4.4% compared with that in 2020). The visitors were from more than 220 countries and regions worldwide, such as the United States, China, and the United Kingdom. Open access (OA) plays a vital role in improving the quality, efficiency, transparency, and integrity of academic journal publishing. From 2019 to 2021, a total of 5543 OA articles were published in the seven journals, of which 2083 (37.6%) were invited and published free-of-charge. During the same period, 1683 articles were published in WJG, and the authors were from more than 70 countries and regions. For the total 5543 articles published in the seven journals from 2019 to 2021, 3903 article quality tracking reports were received after the online publication of these articles. The quality of the articles was further evaluated through the Baishideng's article quality and author evaluation tracking system, with 4655 articles (84.0%) having received author evaluation and feedback, which contributes to tracking metrics for authors' satisfaction with the collective publication processes. From March 25, 2021 to June 28, 2022, the seven journals received a total of 424 reader evaluations and 229 letters from readers; this subsequent reader engagement demonstrates that the popularity of the published articles and the volume of their readership audience were improved through the reader evaluation system. CONCLUSION: Ultimately, the findings from our bibliometric assessments indicate that establishing, promoting and actively practicing processes that safeguard and bolster the integrity of the editing and publication process also help to improve the academic influence of academic journals, which itself is the cornerstone for improving JIF.

Research on risk factors of ischemic cerebrovascular disease in postmenopausal women based on the social-ecological model.

OBJECTIVE: Based on the social-ecological model, this study aimed to comprehensively explore factors affecting the risk of ischemic cerebrovascular disease (ICVD) in postmenopausal women to provide theoretical bases for further prevention and intervention for postmenopausal women. METHODS: Postmenopausal women who underwent medical examinations in one health-checkup agency in Tianjin from May 2015 to October 2015 were enrolled in this study. The ICVD 10-year Risk Assesment Form developed by the research team of the National "Tenth Five-Year Plan" research project was used to assess the factors affecting the risk of ICVD. Based on the social-ecological model, multiple types of scales, including physical activities, depression, Type D personality, social supports, and environment score, were used to comprehensively explore the factors associated with ICVD in postmenopausal women. RESULTS: 300 valid questionnaires were obtained, with an effective rate of 92.0%. The subjects aged 44-74 years, with the average age of 62.06 ± 7.09 years. Among them, 58.67% of the subjects only obtained high-school diploma, 32.67% obtained college or university diploma, 90.33% were retirees, 95.33% were married, 92.33% experienced the natural menopause, 93.33% lived in urban or suburban areas, and 1.00% had a history of breast cancer. Multivariate logistic regression analysis suggested that monthly income (¥), parity, exposure to second-hand or third-hand smoke, easy access to healthy food, physical activities, depression, Type D personality, social support and environmental factors were associated with the risk of ICVD in postmenopausal women (P < 0.05). Among them, easy access to healthy food (OR = 0.242), social support (OR = 0.861) and environmental factors (OR = 0.866) were protective factors from ICVD. OR < 1 indicates that the exposure factor is negatively correlated with the disease, and the exposure factor has a protective effect on preventing the occurrence of the disease. Parity (OR = 3.795), exposure to second-hand or third-hand smoke (OR = 2.886), depression (OR = 1.193), and Type D personality (OR = 1.148) were risk factors of ICVD. OR > 1 means that the exposure factor is positively correlated with the disease, and the exposure factor increases the risk of disease occurrence. CONCLUSIONS: For postmenopausal women, in the future, in addition to prevention and management of the conventional risks, the conditions of their mentality and social support should be paid attention to, at the same time, and if they can, try to choose a good community environment to live in, which could better reduce the incidence and mortality of ICVD in postmenopausal women.

TAK1 is essential for endothelial barrier maintenance and repair after lung vascular injury.

TGF-ß-activated kinase 1 (TAK1) plays crucial roles in innate and adaptive immune responses and is required for embryonic vascular development. However, TAK1's role in regulating vascular barrier integrity is not well defined. Here we show that endothelial TAK1 kinase function is required to maintain and repair the injured lung endothelial barrier. We observed that inhibition of TAK1 with 5Z-7-oxozeaenol markedly reduced expression of ß-catenin (ß-cat) and VE-cadherin at endothelial adherens junctions and augmented protease-activated receptor-1 (PAR-1)- or toll-like receptor-4 (TLR-4)-induced increases in lung vascular permeability. In inducible endothelial cell (EC)-restricted TAK1 knockout (TAK1i∆EC) mice, we observed that the lung endothelial barrier was compromised and in addition, TAK1i∆EC mice exhibited heightened sensitivity to septic shock. Consistent with these findings, we observed dramatically reduced ß-cat expression in lung ECs of TAK1i∆EC mice. Further, either inhibition or knockdown of TAK1 blocked PAR-1- or TLR-4-induced inactivation of glycogen synthase kinase 3ß (GSK3ß), which in turn increased phosphorylation, ubiquitylation, and degradation of ß-cat in ECs to destabilize the endothelial barrier. Importantly, we showed that TAK1 inactivates GSK3ß through AKT activation in ECs. Thus our findings in this study point to the potential of targeting the TAK1-AKT-GSK3ß axis as a therapeutic approach to treat uncontrolled lung vascular leak during sepsis.

Capsella bursa-pastoris (L.) Medic. extract alleviate cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

Systematic characterization of the metabolites of defatted walnut powder extract in vivo and screening of the mechanisms against NAFLD by UPLC-Q-Exactive Orbitrap MS combined with network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored. AIM OF THE STUDY: The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway. MATERIALS AND METHODS: To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies. RESULTS: A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism. CONCLUSION: Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.

Prevalence, clinical correlates and risk factors associated with Tardive Dyskinesia in Chinese patients with schizophrenia.

Tardive Dyskinesia (TD) is a serious, nonrhythmic and iatrogenic movement disorder, and is a common comorbidity in patients with schizophrenia (SZ). The main goal of this study was to investigate the prevalence, clinical correlates, and risk factors of TD in Chinese patients with chronic SZ, which has not been fully studied. This study adopted a cross-sectional design. A total of 901 Chinese inpatients with SZ were recruited between 2008 and 2011. We used the Abnormal Involuntary Movement Scale (AIMS) to measure the severity of TD, and the Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathological symptoms of SZ. Blood samples were also collected for routine blood tests, including the levels of triglyceride (TG), cholesterol (CHO), HDL-cholesterol (HDL-CHO), LDL-cholesterol (LDL-CHO), Apolipoprotein A1 (ApoA1), and Apolipoprotein B (ApoB). Overall, 36% of patients with SZ had TD. Compared with the non-TD patients, the TD patients were more likely to be men, had older age, lower education level, higher smoking rate, higher hospitalization frequency, and longer duration of illness (DOI). Further, compared with the non-TD patients, the TD patients had higher PANSS total, PANSS negative subscale, and cognitive subscale scores, but had lower depressive subscale scores and lower mean levels of metabolic biomarkers, including TG, CHO, HDL-CHO, LDL-CHO, ApoA1 and ApoB. Moreover, binary regression analysis showed that antipsychotic type, BMI, gender, age, HDL-CHO, and ApoB were associated with TD. Our findings indicate that TD is a common movement disorder in patients with chronic SZ, with certain demographic and clinical variables being risk factors for the development of TD.

Comparison of the Effects of Intraperitoneal Injection with Carbon Tetrachloride on Acute Liver Toxicity in Male and Female Kunming Mice.

BACKGROUND Acute chemical liver injury needs to be further explored. The present study aimed to compare the effects of intraperitoneal injection with carbon tetrachloride on acute liver toxicity after 24 h in male and female Kunming mice. MATERIAL AND METHODS In this study, female and male mice were simultaneously divided into 3 different groups. Each group was treated differently, and after 24 h, blood samples were collected to check for changes in the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were used to assess liver toxicity. Liver samples were used for hematoxylin-eosin staining, and periodic acid Schiff reagent staining was performed to detect the pathological changes of each group. The expression level of biomarker molecules in liver cells was also systematically analyzed. RESULTS Our results showed that, compared with male mice, female mice showed more serious damage: reduced glycogen and higher degree of necrosis, and the levels of heatshock protein 27 (HSP27), heat-shock protein 70 (HSP70), proliferating cell nuclear antigen (PCNA) and B cell lymphoma/lewkmia-2 (Bcl-2) were significantly lower than in the male group (P<0.05 or P<0.01), while the results of Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), and cytochrome P450 2E1 (CYP2E1) were the opposite (P<0.05 or P<0.01). CONCLUSIONS The findings from this study showed that, compared with male mice, at 24 h after CCl4 toxicity, female mice showed more severe changes of hepatocyte necrosis and PAS-positivity, with significantly reduced expression of HSP27, HSP70, PCNA, and Bcl-2, and significantly increased expression of Bax, caspase-3, and CYP2E1.

[Effect and mechanism of Bidens pilosa decoction on non-alcoholic fatty liver induced by high fat and high glucose in mice].

This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.

The correlation and role analysis of KCNK2/4/5/15 in Human Papillary Thyroid Carcinoma microenvironment.

Background: KCNKs, potassium two pore domain channel family K members, can maintain the resting potential, regulate the amplitude and duration of the plateau of the action potential, and change the membrane potential and membrane excitability. Evidence from many studies indicates that KCNKs is abnormally expressed in many solid tumors and plays a regulatory role in the development and malignant progression of cancer. However, the expression pattern and prognostic value of KCNK factors in papillary thyroid carcinoma have not been reported. Methods: In this study, we used the data from databases such as ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal to perform bioinformatics analysis of KCNK factors in patients with thyroid cancer. Results: We found that the mRNA expression of KCNK1, KCNK5, KCNK6, KCNK7, and KCNK15 were significantly higher in thyroid cancer tissues than that in normal tissues, while KCNK2, KCNK4, KCNK9, KCNK16 and KCNK17 mRNA levels were decreased compared to normal tissues. And the expression levels of KCNK1/2/4/5/6/7/15 were correlated with the tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that KCNK2/3/4/5/12/15 were associated with overall survival (OS) in patients with thyroid cancer. Conclusion: Finally, the results of ROC curves, immunohistochemical staining, immune cell infiltration and kinase / miRNA / transcription factor regulation showed that KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis. This study implied that KCNK2, KCNK4, KCNK5 and KCNK15 are potential targets of precision therapy for patients with thyroid cancer and these genes are new biomarkers for the therapeutic target for thyroid cancer.

Identification of key genes of papillary thyroid carcinoma by integrated bioinformatics analysis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. METHODS: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein-protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues. RESULTS: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan-Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results. CONCLUSION: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.

[Clinical Efficacy and Prognosis of Double-Hit Multiple Myeloma Patients with Deletion P53 Treated with Regimen Based on Bortezomib].

OBJECTIVE: To investigate the clinical efficacy and prognosis of double-hit multiple myeloma patients with deletion P53 treated with regimen based on bortezomib. METHODS: The ethnical data from 186 newly diagnosed MM patients hospitalized in the Department of Hematology of Harrison International Peace hospital from January 2012 to January 2019 were analyzed retrospectively. The fluorescent in situ hybridization (FISH) and G-binding staining were used to detect cytogenetic abnormalities (P53 deletion, lq21 amplification and IgH rearranagement) for analyses of complete remission (CR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients treated with bortezomib for 4 circles. RESULTS: In 186 patients, simple P53 deletion was 14 cases, 1q21 amplification and P53 deletion were found in 11 cases (A group), t (14;16) and P53 deletion in 7 cases (B group), t (4;14) and P53 deletion in 9 cases (C group). The complete remission rate (CR%) of above-mentioned three groups was 27.27%, 28.57% and 33.33% respectively, and the ORR of the three groups was 54.54%, 57.14% and 55.56%, respectively, there was no statistically significant difference between the three groups (P＞0.05). The patients with 1q21 amplification and P53 deletion had shorter OS and PFS time (P=0.041, P=0.046). The double-hit patients with 1q21 amplification showed shorter OS time, compared with the patients with P53 deletion (P=0.027). The double-hit patients with t(14;16) and t(4;14) showed shorter OS time (P=0.871, P=0.276) and PFS time (P=0.955, P=0.379) than those of the patients with P53 deletion. CONCLUSION: P53 deletion and 1q21 amplification are an adverse prognostic factor of early recurrence and short lifetime in patients with newly diagnosed double-hit MM.

[Clinical Efficacy of Low-Dose Bortezomib-Based Triple Combination Therapy in the Treatment of Elderly Multiple Myeloma].

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose bortezomib-based triple combination therapy in the treatment of elderly multiple myeloma(MM). METHODS: Fifty-eight patients with elderly multiple myeloma were selected. And according to the drug rigimen the patients were randomly divided into three groups. Group A: patients received low-dose bortezomib(0.7mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2,d 4-5, d 8-11, d 11-12. Group B: patients received bortezomib (1.3 mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. Group C: patients received bortezomib(0.7 mg/m2) on day 1, 4, 8 and 11; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. All patients in three groups were treated for 4 circles. The efficacy and response of the three groups were compared. RESULTS: The complete remission (CR) rate in the three groups was 31.58%, 38.09% and 27.78%. And the overall response (ORR) rate of the three groups was 68.42%, 66.67% and 55.56%, there was no statistical difference among the three groups (P＞0.05). The Hb level in MM patients with anemia after treatment was higher than the basic value. There were no statistical differences in percapita red blood cell transfusion, the incidence of bone marrow suppression and infection during 4 courses treatment among 3 groups, but the incidence of peripheral neuropathy, gastrointestinal reaction and herper zoster in group A was significantly lower than that in group B and C, moreover there was statistical difference. After the follow-up for 1 year, there was no significant difference in the survival rate among 3 groups. CONCLUSION: The efficacy of low dose bortezomib-based triple combination therapy for the patients with elderly multiple mycloma is same efficacy as of standard dose bortezomib-based triple combination therapy, but the incidence of perpheral neuropathy, gastrointestinal reaction and herper zoster is lower, the patients have better torelonce to low dose bortezomib-based triple combination therapy regimen, suggesting that this therapy possesses the efficacy of less adverse reactions and more high safety in treatment of patients with elderly muitipe myelome.

Adrenomedullin: an important participant in neurological diseases.

Adrenomedullin, a peptide with multiple physiological functions in nervous system injury and disease, has aroused the interest of researchers. This review summarizes the role of adrenomedullin in neuropathological disorders, including pathological pain, brain injury and nerve regeneration, and their treatment. As a newly characterized pronociceptive mediator, adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain, cancer pain, neuropathic pain induced by spinal nerve injury and diabetic neuropathy. Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance. Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury. Additionally, adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions. Therefore, adrenomedullin is an important participant in nervous system diseases.

Sex Differences in the Prevalence and Clinical Features of Comorbid Depressive Symptoms in Never-Treated Chinese Patients With First-Episode Schizophrenia.

BACKGROUND: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²1 = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (ß = 0.75, t = 7.72, P < .001) and total score (ß = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (ß = 0.74, t = 8.45, P < .001), total score (ß = 0.47, t = 5.71, P < .001), and cognitive factor subscore (ß = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

Acute exacerbation of idiopathic pulmonary fibrosis: usual interstitial pneumonitis vs. possible usual interstitial pneumonitis pattern.

BACKGROUND: The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality. The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT). METHODS: This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016. The subjects were divided into UIP (n = 86) and P-UIP group (n = 21) based on chest HRCT. Continuous variables were analyzed using Student's t test or Mann-Whitney U test. Categorical variables were analyzed using χ test. Log-rank test was used for the survival analysis. Cox proportional models evaluated the risk factors for AE occurrence and survival. RESULTS: The male, older patients, previous N-acetylcysteine use, elevated white blood cell (WBC) counts, and microbiology infection were more common in the UIP group than the P-UIP group (χ = 13.567, P < 0.001; z = -2.936, P = 0.003; χ = 5.901, P = 0.015; t = 2.048, P = 0.043; χ = 10.297, P = 0.036, respectively). The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (IIP) was significantly higher than P-UIP pattern (χ = 40.011, P < 0.001). Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group. The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (χ = 5.489, P = 0.019) despite of the similar overall survival in the two groups. Multivariate Cox regression analysis indicated WBC count, partial pressure of oxygen in artery (PaO2)/fractional concentration of inspired oxygen (FiO2), and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]: 1.070, 95% confidential interval [CI]: 1.027-1.114, P = 0.001; HR: 0.992, 95% CI: 0.986-0.997, P = 0.002; and HR: 1.649, 95% CI: 1.253-2.171, P < 0.001, respectively). CONCLUSIONS: AE occurrence of UIP patients in IIP was significantly more than P-UIP cases. The short-term survival was better in the UIP group despite of the similar overall survival in the two groups. WBC count, PaO2/FiO2, and CT score were the independent predictors for survival in UIP subjects.

[Significance of Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the significance of neutrophil/lymphocyte ratio(NLR) and platelet/lymphocyte ratio(PLR) in patients with multiple myeloma (MM). METHODS: Eighty patients with multiple myeloma admitted in our hospital from August 2007 to August 2010 were selected. The clinical data of the patients, including hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), white blood cell(WBC) count, absolute neutrophil count (ANC), platelet count (PC), glomerular filtration rate (GFR), calcium, albumin, ß2 microglobulin and so on were collected and analyzed. RESULTS: The optimal threshold of NLR was 2.78 (sensitivity: 83.3%, specificity: 43.1%). The optimal threshold of PLR was 155.58 (sensitivity: 67.7%, specificity: 36.9%). All patients were grouped according to NLR and PLR values, patients with high NLR and PLR had lower albumin levels and higher clinical stages. High NLR patients were mainly men, hemoglobin, GFR values, albumin levels were lower, and the white blood cells count and ß2 microglobulin level were higher. High PLR patients showed low albumin level and higher clinical stage. Multivariate analysis showed that ß2 microglobulin and NLR were prognostic factors in patients with multiple myeloma (P<0.05). Kaplan-Meier survival analysis showed that the median survival time was 37 months (95% CI: 21.80-52.19) for patients with high NLR and 66 months (95% CI: 53.19-78.80) for patients with low NLR. The median survival time was 45 months (95% CI: 0.00 to 91.18) in patients with high PLR and 62 months (95% CI: 45.67-78.33) in patients with low PLR. CONCLUSION: High NLR (>2.78) associates with poor prognosis in patients with MM, and it may be considered as an independent prognostic factor for MM patients.