Peripheral Blood Markers Predictive of Progression-Free Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Treated With PD-1 Inhibitors Plus Chemotherapy as First-Line Therapy.

Aim: To determine the prognostic value of peripheral blood markers in advanced esophageal squamous cell carcinoma (ESCC) patients receiving programmed cell death protein 1 inhibitors plus chemotherapy as first-line therapy. Methods: A retrospective analysis of 54 patients with advanced ESCC was performed to assess 12 blood markers involving inflammation, nutrition, and tumor burden. Analysis of variance or Kruskal-Wallis tests were used to explore the difference in markers among different response to therapy. Survival curves were constructed using the Kaplan-Meier method. Multivariate Cox models were applied to identify independent predictors of outcome. Results: Patients who achieved response had significantly higher prealbumin, increased BMI, and lower hs-CRP levels at baseline compared with those who experienced disease progression. In the univariate analysis, ALI > 23.55, PNI > 45.175, NLR ≤ 5, and hs-CRP ≤ 6.7 mg/L were significantly associated with a better progression-free survival. Cox regression analysis revealed that ALI >23.55 (P = 0.037) and hs-CRP ≤6.7 mg/L (P = 0.043) were independently associated with superior PFS. Increased tumor abnormal protein (TAP) levels post two cycles was significantly associated with a worse prognosis (P = 0.004). Conclusions: A baseline signature of low ALI and high hs-CRP as well as an early increase in TAP in ESCC appear to be predictive of inferior PFS.

Development of a Speech-based Composite Score for Remotely Quantifying Language Changes in Frontotemporal Dementia.

BACKGROUND: Changes to speech and language are common symptoms across different subtypes of frontotemporal dementia (FTD). These changes affect the ability to communicate, impacting everyday functions. Accurately assessing these changes may help clinicians to track disease progression and detect response to treatment. OBJECTIVE: To determine which aspects of speech show significant change over time and to develop a novel composite score for tracking speech and language decline in individuals with FTD. METHOD: We recruited individuals with FTD to complete remote digital speech assessments based on a picture description task. Speech samples were analyzed to derive acoustic and linguistic measures of speech and language, which were tested for longitudinal change over the course of the study and were used to compute a novel composite score. RESULTS: Thirty-six (16 F, 20 M; M age = 61.3 years) individuals were enrolled in the study, with 27 completing a follow-up assessment 12 months later. We identified eight variables reflecting different aspects of language that showed longitudinal decline in the FTD clinical syndrome subtypes and developed a novel composite score based on these variables. The resulting composite score demonstrated a significant effect of change over time, high test-retest reliability, and a correlation with standard scores on various other speech tasks. CONCLUSION: Remote digital speech assessments have the potential to characterize speech and language abilities in individuals with FTD, reducing the burden of clinical assessments while providing a novel measure of speech and language abilities that is sensitive to disease and relevant to everyday function.

M2-phenotype tumour-associated macrophages upregulate the expression of prognostic predictors MMP14 and INHBA in pancreatic cancer.

Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.

Tumor-associated macrophages promote the metastasis and growth of non-small-cell lung cancer cells through NF-κB/PP2Ac-positive feedback loop.

Non-small-cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor-associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor-associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage-conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF-κB pathway-dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF-κB pathway signaling. Overexpression of PP2Ac, or the dominant-negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF-κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration.

Hepatic Encephalopathy is Associated With Slow Speech on Objective Assessment.

INTRODUCTION: There are no available low-burden, point-of-care tests to diagnose, grade, and predict hepatic encephalopathy (HE). METHODS: We evaluated speech as a biomarker of HE in 76 English-speaking adults with cirrhosis. RESULTS: Three speech features significantly correlated with the following neuropsychiatric scores: speech rate, word duration, and use of particles. Patients with low neuropsychiatric scores had slower speech (22 words/min, P = 0.01), longer word duration (0.09 seconds/word, P = 0.01), and used fewer particles (0.85% fewer, P = 0.01). Patients with a history of overt HE had slower speech (23 words/min, P = 0.005) and longer word duration (0.09 seconds/word, P = 0.005). DISCUSSION: HE is associated with slower speech.

Lung Auscultation of Hospitalized Patients with SARS-CoV-2 Pneumonia via a Wireless Stethoscope.

Objective: SARS-CoV-2 (originally named COVID-2019) pneumonia is currently prevalent worldwide. The number of cases has increased rapidly but the auscultatory characteristics of affected patients and how to use it to predict who is most likely to survive or die are not available. This study aims to describe the auscultatory characteristics and its clinical relativity of SARS-CoV-2 pneumonia by using a wireless stethoscope. Material and methods: A cross-sectional, observational, single-center case series of 30 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia at Leishenshan Hospital in Wuhan, China, were enrolled from March 9 to April 5, 2020. Clinical, laboratory, radiological, treatment data and lung auscultation were collected and analyzed. Lung auscultation was acquired by a wireless electronic stethoscope. Auscultatory characteristics of the moderate, severe, and critically ill patients were compared. Results: Kinds of crackles including fine crackles and wheezing were heard and recorded in these patients. Velcro crackles were heard in most critically ill patients (6/10). Besides, patients with Velcro crackles were all dead (6/6). There was no positive lung auscultatory finding in the moderate group and little positive lung auscultatory findings (4/10) in the severe group. Conclusion: Velcro crackles can be auscultated by this newly designed electronic wireless stethoscope in most critically ill patients infected by SARS-CoV-2 and predicts a poor prognosis. Moderate and severe patients without positive auscultatory findings may have a better prognosis.

VEGFR2 promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer.

BACKGROUND: VEGF/VEGFR2 pathway is the central therapeutic target in anti-angiogenic treatment in multiple cancers. However, little work has been carried out concerning the pro-malignancy functions of VEGFR2 that are independent of its pro-angiogenesis effects in gastric cancer. Here, we demonstrated that VEGFR2 up-regulation in gastric cancer tissues was a prognostic marker for poor disease-free survival and overall survival of gastric cancer patients. METHODS: Immunohistochemistry was used to detect VEGFR2 and VTN expressions in specimens. Kaplan-Meier curves were constructed for survival analysis. Stably knockdown cell lines and overexpression cell lines were constructed by small interfering RNA and plasmids transfection. Real-time PCR and Western blot were used to confirm the expressions of target genes at both RNA and protein levels. Cell proliferation was measured by using Cell Counting Kit-8 and xenograft models. Microarray and bioinformatic analysis were also performed to identify the relationship between Vitronectin (VTN) and VEGFR2. RESULTS: When overexpressed in gastric cancer cells, VEGFR2 increased cellular proliferation and invasion in vitro and tumor formation in xenograft models. By using integrating microarray and bioinformatic analysis, we identifiedVTN as a downstream of VEGFR2 pathway. In gain- and loss-of function analysis in gastric cancer cells, VTN was further verified in consistent with VEGFR2 in expression levels and in regulating cell growth and motility in vitro and in vivo. Moreover, in gastric cancer samples, VTN was as also revealed as a poor prognostic factor. CONCLUSIONS: Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects. IMPLICATIONS: Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects, which may provide a new and valuable target for design of therapies for intervention and a new cognitive perspective for the anti-angiogenesis therapies.

The radiotherapy-sensitization effect of cantharidin: Mechanisms involving cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair.

BACKGROUND: Cantharidin is an inhibitor of protein phosphatase 2 A (PP2A), and has been frequently used in clinical practice. In our previous study, we proved that cantharidin could arrest cell cycle in G2/M phase. Since cells at G2/M phase are sensitive to radiotherapy, in the present study, we investigated the radiotherapy-sesitization effect of cantharidin and the potential mechanisms involved. METHODS: Cell growth was determined by MTT assay. Cell cycle was evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X staining. Expression of mRNA was tested by microarray assay and real-time PCR. Clinical information and RNA-Seq expression data were derived from The Cancer Genome Atlas (TCGA) pancreatic cancer cohort. Survival analysis was obtained by Kaplan-Meier estimates. RESULTS: Cantharidin strengthened the growth inhibition effect of irradiation. Cantharidin drove pancreatic cancer cells out of quiescent G0/G1 phase and arrested cell cycle in G2/M phase. As a result, cantharidin strengthened DNA damage which was induced by irradiation. Moreover, cantharidin repressed expressions of several genes participating in DNA damage repair, including UBE2T, RPA1, GTF2HH5, LIG1, POLD3, RMI2, XRCC1, PRKDC, FANC1, FAAP100, RAD50, RAD51D, RAD51B and DMC1, through JNK, ERK, PKC, p38 and/or NF-κB pathway dependent manners. Among these genes, worse overall survival for pancreatic cancer patients were associated with high mRNA expressions of POLD3, RMI2, PRKDC, FANC1, RAD50 and RAD51B, all of which could be down-regulated by cantharidin. CONCLUSION: Cantharidin can sensitize pancreatic cancer cells to radiotherapy. Multiple mechanisms, including cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair, may be involved.

The values of applying classification and counts of white blood cells to the prognostic evaluation of resectable gastric cancers.

BACKGROUND: The classifications and counts of white blood cells (WBCs) have been proved to be able to be used as prognostic markers in cancer cases. The present study investigated the potential values of the classifications and counts of WBC, including lymphocyte (LY), monocyte (MO), neutrophil (NE), eosinophil (EO), and basophil (BA) in the prognosis of resectable gastric cancers (GCs). METHODS: This retrospective study recruited 104 resectable GC cases which were pathologically confirmed. The patients were divided into two groups according to the median pre-treatment values. To evaluate the changes in WBC counts and classification after treatment, we introduced the concept of post/pre-treatment ratios (≤ 1 indicated count was not increased after therapy, while > 1 suggested increased count). RESULTS: Pre-treatment NE and total WBC counts were negatively correlated with overall survival (OS). Surgery significantly decreased the level of NE count, but increased the level of EO, whereas had no effect on the levels of LY, MO, BAor total WBC. Adjuvant chemotherapy significantly decreased the level of BA. Whole course of treatment (surgery combined with adjuvant chemotherapy) had no significant effect on the counts of LY, MO, NE, EO, BA or total WBC. Post/pre-treatment ratios of LY, MO NE, EO, BA and total WBC levels had no effects on OS. Univariate analysis indicated that AJCC stage (III) and higher level of pre-treatment total WBC count were prognostic factors affecting OS. Multivariate Cox regression analysis revealed that AJCC stage (III) and higher level of pre-treatment total WBC count were independent prognostic factors. CONCLUSIONS: Pre-treatment NE count and pre-treatment total WBC count may be potential prognostic factors for the prognostic evaluation of GCs.

TNF-α sensitizes chemotherapy and radiotherapy against breast cancer cells.

PURPOSE: Despite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells. METHODS: Cell growth was determined by MTT assay in vitro, and by using nude mouse tumor xenograft model in vivo. Cell cycle and apoptosis/necrosis were evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X staining. mRNA expression was assessed by using real-time PCR. Protein expression was tested by Western blot assay. RESULTS: TNF-α strengthened the cytotoxicity of docetaxel, 5-FU and cisplatin against breast cancer cells both in vitro and in vivo. TNF-α activated NF-κB pathway and dependently up-regulated expressions of CyclinD1, CyclinD2, CyclinE, CDK2, CDK4 and CDK6, the key regulators participating in G1→S phase transition. As a result, TNF-α drove cells out of quiescent G0/G1 phase, entering vulnerable proliferating phases. Treatment of TNF-α brought more DNA damage after Cs137-irradiation and strengthened G2/M and S phase cell cycle arrest induced by docetaxel and cisplatin respectively. Moreover, the up-regulation of RIP3 (a necroptosis marker) by 5-FU, and the activation of RIP3 by TNF-α, synergistically triggered necroptosis (programmed necrosis). Knockdown of RIP3 attenuated the synergetic effect of TNF-α and 5-FU. CONCLUSION: TNF-α presented radiotherapy- and chemotherapy-sensitizing effects against breast cancer cells.

Psychogenic fever in a patient with small cell lung cancer: a case report.

BACKGROUND: Fever is common in malignant tumors. We report an exceptional case of psychogenic fever in a patient with small cell lung cancer. This is the first case report of psychogenic fever in a patient with small cell lung cancer. CASE PRESENTATION: A 61-year-old Chinese man diagnosed with small cell carcinoma on June 30, 2012, came to our department with a complaint of fever lasting more than 1 month. He had undergone chemoradiotherapy for lung cancer 6 months previously. After admission, his body temperature fluctuated in the range of 37 °C to 39 °C. Somatic symptoms associated with anxiety were obvious. A 24-item Hamilton Anxiety Scale was used to assess the patient's condition. A score of 32 confirmed a diagnosis of severe anxiety. After a week of antianxiety treatment, the patient's temperature returned to normal. CONCLUSION: Psychogenic fever is common in cancer patients and deserves more attention. Patients with psychogenic fever must be distinguished from patients with infectious fever (including neutropenic fever), and tumor fever. Additionally, antianxiety or antidepression treatment should be provided. A concern is that continual anxiety may adversely affect anticancer therapy.

The opportunities and challenges of using PD-1/PD-L1 inhibitors for leukemia treatment.

Leukemia poses a significant clinical challenge due to its swift onset, rapid progression, and treatment-related complications. Tumor immune evasion, facilitated by immune checkpoints like programmed death receptor 1/programmed death receptor ligand 1 (PD-1/PD-L1), plays a critical role in leukemia pathogenesis and progression. In this review, we summarized the research progress and therapeutic potential of PD-L1 in leukemia, focusing on targeted therapy and immunotherapy. Recent clinical trials have demonstrated promising outcomes with PD-L1 inhibitors, highlighting their role in enhancing treatment efficacy. This review discusses the implications of PD-L1 expression levels on treatment response and long-term survival rates in leukemia patients. Furthermore, we address the challenges and opportunities in immunotherapy, emphasizing the need for personalized approaches and combination therapies to optimize PD-L1 inhibition in leukemia management. Future research prospects include exploring novel treatment strategies and addressing immune-related adverse events to improve clinical outcomes in leukemia. Overall, this review provides valuable insights into the role of PD-L1 in leukemia and its potential as a therapeutic target in the evolving landscape of leukemia treatment.

Improvement of in vivo iron bioavailability using mung bean peptide-ferrous chelate.

There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO4), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO4 (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO4) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 (Divalent metal transporter 1), Fpn 1 (Ferroportin 1), and Dcytb (Duodenal cytochrome b) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.

Peptide composition analysis, structural characterization, and prediction of iron binding modes of small molecular weight peptides from mung bean.

Iron supplementation is a proactive approach to limit instances of iron deficiency anemia. This study is based on the enzymatic hydrolysis and fractionation of mung bean proteins (MBPs) followed by the determination of the Fe2+ chelating activities of these peptide-containing fractions. MBP-Fe complex was generated using a chemical chelation method and subsequently characterized. Following Sephadex G15 separation of MBPs, one of the fractions containing 10 different peptides, demonstrated maximum Fe2+ chelating activity of 39.97 ± 0.07 µg/mg. The sequences of these peptides were determined using liquid chromatography-tandem mass spectrometry. The Fe2+ ion content of the MBP-Fe complex was determined using X-ray photoelectron spectroscopy and 80% of the iron was found to be in Fe2+ oxidation state. After iron chelation, there was an increase in the peptide's particle size, with an average value of 550.67 ± 0.70 nm. This increase in size was attributed to the contributions of the amino proline and glycine, which extended the peptides to form the MBP-Fe complex. Finally, molecular docking studies revealed that Fe2+ mainly bound to carboxy-oxygen of glutamate and aspartate residues of mung bean peptides to form MBP-Fe complex. This research could serve as a scientific foundation for the development of dietary iron supplements using plant-derived peptides.

Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment.

Melanoma, the most aggressive form of cutaneous malignancy arising from melanocytes, is frequently characterized by metastasis. Despite considerable progress in melanoma therapies, patients with advanced-stage disease often have a poor prognosis due to the limited efficacy, off-target effects, and toxicity associated with conventional drugs. Nanotechnology has emerged as a promising approach to address these challenges with nanoparticles capable of delivering therapeutic agents specifically to the tumor microenvironment (TME). However, the clinical approval of nanomedicines for melanoma treatment remains limited, necessitating further research to develop nanoparticles with improved biocompatibility and precise targeting capabilities. This comprehensive review provides an overview of the current research on nano-drug delivery systems for melanoma treatment, focusing on liposomes, polymeric nanoparticles, and inorganic nanoparticles. It discusses the potential of these nanoparticles for targeted drug delivery, as well as their ability to enhance the efficacy of conventional drugs while minimizing toxicity. Furthermore, this review emphasizes the significance of interdisciplinary collaboration between researchers from various fields to advance the development of nanomedicines. Overall, this review serves as a valuable resource for researchers and clinicians interested in the potential of nano-drug delivery systems for melanoma treatment and offers insights into future directions for research in this field.

Intensive blood pressure lowering and the risk of new-onset diabetes in patients with hypertension: a post-hoc analysis of the STEP randomized trial.

AIMS: The strategy of blood pressure intervention in the elderly hypertensive patients (STEP) trial reported the cardiovascular benefit of intensive systolic blood pressure (SBP) control in patients with hypertension. The association between intensive SBP lowering and the risk of new-onset diabetes is unclear. This study aimed to evaluate the effect of intensive SBP lowering on the incidence of new-onset diabetes. METHODS AND RESULTS: Participants in STEP who had baseline fasting serum glucose (FSG) concentrations <7.0 mmol/L and no history of diabetes or hypoglycaemic medication use were included. The primary outcome was new-onset diabetes defined as the time to first occurrence of FSG concentrations ≥7.0 mmol/L. The secondary outcome was new-onset impaired fasting glucose (FSG: 5.6-6.9 mmol/L) in participants with normoglycemia. A competing risk proportional hazards regression model was used for analysis. The cohort comprised 5601 participants (mean age: 66.1 years) with a mean baseline SBP of 145.9 mmHg. Over a median follow-up of 3.42 years, 273 (9.6%) patients in the intensive SBP group (target, 110 to <130 mmHg) and 262 (9.5%) in the standard SBP group (target, 130 to <150 mmHg) developed diabetes (adjusted hazard ratio, 1.01; 95% confidence interval (CI), 0.86-1.20). The adjusted hazard ratio for the secondary outcome was 1.04 (95% CI, 0.91-1.18). The mean highest FSG concentration during the follow-up was 5.82 and 5.84 mmol/L in the intensive and standard groups, respectively. CONCLUSION: Intensive SBP lowering is not associated with an altered risk of new-onset diabetes or impaired fasting glucose in hypertensive patients. REGISTRATION: STEP ClinicalTrials.gov, number: NCT03015311.

There is no significant association between intensive SBP lowering and the risk of new-onset diabetes or impaired fasting glucose in hypertensive patients aged 60­80 years.Our findings improve the understanding of the benefits and risks of implementing an intensive SBP treatment strategy in the clinic for older hypertensive patients.Our findings suggest that clinicians should continue to implement intensive SBP lowering strategies, without worrying about an altered risk of new-onset diabetes in their patients.

Pharmacovigilance for rare diseases: a bibliometrics and knowledge-map analysis based on web of science.

OBJECTIVES: The aims of this paper is to search and explore publications in the field of pharmacovigilance for rare diseases and to visualize general information, research hotspots, frontiers and future trends in the field using the bibliometric tool CiteSpace to provide evidence-based evidence for scholars. METHODS: We searched the Web of Science Core Collection (WoSCC) for studies related to pharmacovigilance for rare diseases, spanning January 1, 1997-October 25, 2022. CiteSpace software was utilized to discuss countries/regions, institutions, authors, journals, and keywords. RESULTS: After screening, a total of 599 valid publications were included in this study, with a significant upward trend in the number of publications. These studies were from 68 countries/regions with the United States and the United Kingdom making the largest contributions to the field. 4,806 research scholars from 493 institutions conducted studies on pharmacovigilance for rare diseases. Harvard University and University of California were the top two productive institutions in the research field. He Dian of the Affiliated Hospital of Guizhou Medical University and Peter G.M. Mol of the University of Groningen, The Netherlands, were the two most prolific researchers. The Cochrane Database of Systematic Reviews and the New England Journal of Medicine were the journals with the highest number of articles and co-citation frequency respectively. Clinical trial, therapy and adverse event were the top three most cited keywords. CONCLUSIONS: Based on keywords co-occurrence analysis, four research topics were identified: orphan drug clinical trials, postmarketing ADR surveillance for orphan drugs, rare diseases and orphan drug management, and diagnosis and treatment of rare diseases. Immune-related adverse reactions and benefit-risk assessment of enzyme replacement therapy were at the forefront of research in this field. Treatment outcomes, early diagnosis and natural history studies of rare diseases may become hotspots for future research.

Evaluating the utility of daily speech assessments for monitoring depression symptoms.

Objective: Depression is a common mental health disorder and a major public health concern, significantly interfering with the lives of those affected. The complex clinical presentation of depression complicates symptom assessments. Day-to-day fluctuations of depression symptoms within an individual bring an additional barrier, since infrequent testing may not reveal symptom fluctuation. Digital measures such as speech can facilitate daily objective symptom evaluation. Here, we evaluated the effectiveness of daily speech assessment in characterizing speech fluctuations in the context of depression symptoms, which can be completed remotely, at a low cost and with relatively low administrative resources. Methods: Community volunteers (N = 16) completed a daily speech assessment, using the Winterlight Speech App, and Patient Health Questionnaire-9 (PHQ-9) for 30 consecutive business days. We calculated 230 acoustic and 290 linguistic features from individual's speech and investigated their relationship to depression symptoms at the intra-individual level through repeated measures analyses. Results: We observed that depression symptoms were linked to linguistic features, such as less frequent use of dominant and positive words. Greater depression symptomatology was also significantly correlated with acoustic features: reduced variability in speech intensity and increased jitter. Conclusions: Our findings support the feasibility of using acoustic and linguistic features as a measure of depression symptoms and propose daily speech assessment as a tool for better characterization of symptom fluctuations.

Lipopolysaccharide (LPS) extracted from Bacteroides vulgatus effectively prevents LPS extracted from Escherichia coli from inducing epithelial­mesenchymal transition.

Pathological epithelial­mesenchymal transition (EMT) has been shown to fulfill a key role in the development and progression of a variety of lung diseases. It has been demonstrated that the inflammatory microenvironment is a decisive factor in inducing pathological EMT. Hexacylated lipopolysaccharide (LPS) [or proacylated lipopolysaccharide (P­LPS), which functions as proinflammatory lipopolysaccharide] is one of the most effective Toll­like receptor 4 (TLR4) agonists. Furthermore, the pentacylated and tetracylated form of lipopolysaccharide (or A­LPS, which functions as anti­inflammatory lipopolysaccharide) has been shown to elicit competitive antagonistic effects against the pro­inflammatory activity of P­LPS. At present, it remains unclear whether LPS extracted from Bacteroides vulgatus (BV­LPS) can prevent LPS extracted from Escherichia coli (EC­LPS) from inducing pathological EMT. In the present study, A549 cells and C57BL/6 mice lung tissue were both induced by EC­LPS (P­LPS) and BV­LPS (A­LPS), either alone or in combination. The anticipated anti­inflammatory effects of BV­LPS were analyzed by examining the lung coefficient, lung pathology, A549 cell morphology and expression levels both of the inflammatory cytokines, IL­1ß, IL­6 and TNF­α and of the EMT signature proteins, epithelial cadherin (E­cadherin), α­smooth muscle actin (α­SMA) and vimentin. In addition, the expression levels of TLR4, bone morphogenic protein and activin membrane­bound inhibitor (BAMBI) and Snail were detected and the possible mechanism underlying how BV­LPS may prevent EC­LPS­induced EMT was analyzed. The results obtained showed that the morphology of the A549 cells was significantly polarized, the lung index was significantly increased, the alveolar structure was collapsed and the expression levels of IL­1ß, IL­6, TNF­α, α­SMA, vimentin, TLR4 and Snail in both lung tissue and A549 cells were significantly increased, whereas those of E­cadherin and BAMBI were significantly decreased. Treatment with BV­LPS in combination with EC­LPS was found to reverse these changes. In conclusion, the present study demonstrated that BV­LPS is able to effectively prevent EC­LPS­induced EMT in A549 cells and in mouse lung tissue and furthermore, the underlying mechanism may be associated with inhibition of the TLR4/BAMBI/Snail signaling pathway.

The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study.

Sleep can affect nonalcoholic fatty liver disease (NAFLD). We investigated the association between sleep duration, sleep quality, and NAFLD. From January to December 2018, 1,073 patients (age: 37.94 ± 10.88, Body Mass Index (BMI): 22.85 ± 3.27) were enrolled. Pittsburgh Sleep Quality Index Questionnaire and Munich Chronotype Questionnaire were used to assess sleep duration, quality, and habits. Ultrasonography was used to diagnose NAFLD. Multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the risk of NAFLD by different types of sleep duration and sleep quality. No significant differences in sleep time, sleep quality, and sleep habits between the NAFLD and the non-NAFLD groups were observed (P > 0.05). There was no correlation between sleep duration and NAFLD in the whole cohort. After adjusting for age, exercise, fasting plasma glucose, and BMI, the group with long sleep duration showed a decreased risk of NAFLD in men (OR = 0.01, 95% CI: 0.001-0.27, P = 0.032). However, in all four adjusted models, no correlation between sleep duration, quality, and NAFLD was found in women. In conclusion, sleep duration was significantly and negatively associated with NAFLD in men but not women. Prospective studies are required to confirm this association.