Experiences of patients with advanced cancer coping with chronic pain: a qualitative analysis.

OBJECTIVES: To gain insight into the perceptions, and beliefs of patients with advanced cancer coping with chronic pain and to identify their attitudes and demands on pain management. METHODS: From July to September 2022, 17 patients with advanced cancer living with chronic pain were recruited from a tertiary cancer hospital in Hunan Province, China. Qualitative and semi-structured interviews were conducted individually, with 30-45 minutes for each. The Colaizzi 7-step analysis method in phenomenological research was used for data analysis. RESULTS: The experience of pain acceptance by advanced cancer patients with chronic pain was summarized into four themes: pain catastrophizing (unable to ignore the pain, try various methods to relieve the pain, exaggerating pain perception, and lack of knowledge about proper pain management), rumination (compulsive rumination and worrying rumination), avoidance coping (situational avoidance and repressive avoidance) and constructive action (setting clear value goal and taking reciprocal action). CONCLUSION: Most patients with advanced cancer had low pain acceptance and negative attitudes. Feeling helpless in the face of pain and suffering alone were their norm. Long-term negative emotions could lead to gradual depression and loss of hope for treatment, resulting in pain catastrophizing and persistent rumination. Nevertheless, a few patients accepted pain with positive attitudes. Medical professionals should pay more attention to the psychological status of advanced cancer patients with chronic pain, and employ alternative therapies, for example, cognitive behavioral therapy. More efforts are needed to reduce patients' pain catastrophizing, and promote their pain acceptance by a better understanding of pain through health education.

[Research Status and Trend of Screening for Women's Common Diseases in China].

Objective To visualize the research status and hotspots of women's common disease screening based on CiteSpace 6.1.R6,and to provide a reference for the in-depth research in this field thereafter. Methods The relevant articles were retrieved from the China National Knowledge Infrastructure with the time interval from January 1,1992 to December 13,2022.The analysis was conducted on the number of annual publications,countries(regions),institutions,author collaboration networks,keyword co-occurrence,clustering,and bursts. Results A total of 900 papers that met the criteria were included,and the number of annual publications showed a trend of first increasing and then decreasing.The cross-institutional collaboration network was mature.The research hotspots mainly covered women's health,the prevalence of women's diseases,reproductive health,and breast diseases.The hotspots have evolved from an initial focus on reproductive health care to gynecological disease management,and eventually to reproductive health and holistic health care in women. Conclusions The attention should be kept on the screening of women's common diseases.It is advisable to synchronize the screening of women's common diseases with the screening of cervical and breast cancers to expand the screening coverage,promote early disease detection and treatment,and comprehensively safeguard women's health.

Gene co-expression network analysis in areca floral organ and the potential role of the AcMADS17 and AcMADS23 in transgenic Arabidopsis.

Areca catechu L., a monocot belonging to the palm family, is monoecious, with female and male flowers separately distributed on the same inflorescence. To discover the molecular mechanism of flower development in Areca, we sequenced different floral samples to generate tissue-specific transcriptomic profiles. We conducted a comparative analysis of the transcriptomic profiles of apical sections of the inflorescence with male flowers and the basal section of the inflorescence with female flowers. Based on the RNA sequencing dataset, we applied weighted gene co-expression network analysis (WGCNA) to identify sepal, petal, stamen, stigma and other specific modules as well as hub genes involved in specific floral organ development. The syntenic and expression patterns of AcMADS-box genes were analyzed in detail. Furthermore, we analyzed the open chromatin regions and transcription factor PI binding sites in male and female flowers by assay for transposase-accessible chromatin sequencing (ATAC-seq) assay. Heterologous expression revealed the important role of AcMADS17 and AcMADS23 in floral organ development. Our results provide a valuable genomic resource for the functional analysis of floral organ development in Areca.

Diosgenin as a substitute for cholesterol alleviates NAFLD by affecting CYP7A1 and NPC1L1-related pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NAFLD treatment. Diosgenin as the structural analogue of cholesterol attenuates hypercholesterolemia by inhibiting cholesterol metabolism, which is an important pathogenesis in NAFLD progression. However, there has been no few report concerning its effects on NAFLD so far. METHODS: Using a high-fat diet & 10% fructose-feeding mice, we evaluated the anti-NAFLD effects of diosgenin. Transcriptome sequencing, LC/MS analysis, molecular docking simulation, molecular dynamics simulations and Luci fluorescent reporter gene analysis were used to evaluate pathways related to cholesterol metabolism. RESULTS: Diosgenin treatment ameliorated hepatic dysfunction and inhibited NAFLD formation including lipid accumulation, inflammation aggregation and fibrosis formation through regulating cholesterol metabolism. For the first time, diosgenin was structurally similar to cholesterol, down-regulated expression of CYP7A1 and regulated cholesterol metabolism in the liver (p < 0.01) and further affecting bile acids like CDCA, CA and TCA in the liver and feces. Besides, diosgenin decreased expression of NPC1L1 and suppressed cholesterol transport (p < 0.05). Molecular docking and molecular dynamics further proved that diosgenin was more strongly bound to CYP7A1. Luci fluorescent reporter gene analysis revealed that diosgenin concentration-dependently inhibited the enzymes activity of CYP7A1. CONCLUSION: Our findings demonstrated that diosgenin was identified as a specific regulator of cholesterol metabolism, which pave way for the design of novel clinical therapeutic strategies.

Gut liver brain axis in diseases: the implications for therapeutic interventions.

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, ß-amyloid (Aß) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aß metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

Dual-mode vortex beam transmission metasurface antenna based on linear-to-circular polarization converter.

The generation of multi-mode vortex beams at the same aperture is currently emerging as a research hotspot. In this paper, a method based on a linearly polarized-circularly polarized translational transmission metasurface (TM) is proposed to enable a dual-circularly polarized dual-mode vortex beam generation. Through the judicious implementation of an additional rotational phase and the combination of the initial transmission phase, the phases of the left-hand circularly polarized (LHCP) and right-hand circularly polarized (RHCP) waves can be manipulated arbitrarily and independently. Meanwhile, the design of the array phase is utilized for the dual-mode dual-circularly polarized beam generation. Simulation and sample measurements provide validation data for the feasibility of this method, in which the measurement results are in excellent consistency with the simulation ones. This proposed method paves the way toward the enhancement of the channel capacity of mobile communication.

Psychometric validation of the modified Chinese version of the personalized psychological flexibility index in patients with cancer.

Objective: The aim of this study was to perform across-cultural adaptation of the English version of the personalized psychological flexibility index (PPFI) into Chinese, and to evaluate its psychometric properties in patients with cancer. Methods: This study was conducted in two phases. In phase 1, we followed Beaton's guidelines for cross-cultural adaptation of PPFI. In phase 2, we conducted a cross-sectional study to assess the validity and reliability of the PPFI among a total of 455 patients with cancer in Hunan Province of China. Item analysis was used to evaluate and screen items, while content validity, construct validity, convergent validity, and concurrent validity were used to evaluate the validity. Reliability was assessed using Cronbach's ɑ coefficient, retest reliability, and composite reliability. Results: The item-level content validity index of the modified Chinese version of PPFI (PPFI-C) ranged from 0.89 to 1.00, the scale-level CVI/universal agreement was 0.87, and the S-CVI/average was 0.99. Exploratory factor analysis identified a 14-item, three-factor structure of PPFI (item 11 deleted). Confirmatory factor analysis showed χ2/df â€‹= â€‹2.42, RMSEA â€‹= â€‹0.07, GFI â€‹= â€‹0.92, NFI â€‹= â€‹0.91, TLI â€‹= â€‹0.93, CFI â€‹= â€‹0.95, and IFI â€‹= â€‹0.95. PPFI-C demonstrated positive correlations with the 8-item Commitment Action Questionnaire, and negative correlations with Acceptance and Action Questionnaire-II, Hospital Anxiety and Depression Scale, and Short Form Quality Life Scale. The Cronbach's ɑ coefficient of modified PPFI-C stood at 0.84. Conclusions: The results suggest that the 14-item PPFI-C is a reliable and valid tool for measuring PF in Chinese patients with cancer. However, additional studies are needed to validate the psychometric properties of PPFI-C in other populations.

Reliability and validity of the Chinese version of the Sakata Eating Behavior Scale short form and preliminary analysis of the factors related to the score of the scale.

Background: The obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan. Objective: To translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors. Method: The EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores. Result: Among 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36-50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form. Conclusion: The structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.

Effectiveness of virtual reality technology in symptom management of end-of-life patients: protocol of a systematic review and meta-analysis.

INTRODUCTION: With the worsening of population ageing globally, the number of the elderly with chronic and incurable diseases such as malignant tumours is gradually increasing, and the need for palliative care is growing. As a primary task in the end-of-life phase, symptom management is an essential aspect of palliative care, which aims to alleviate distressing symptoms of terminally ill patients and improve their quality of life. Virtual reality (VR) technology, which allows the creation of simulated environments in which a three-dimensional experience is generated, has been increasingly used in palliative care for symptom management. Therefore, we aim to conduct a systematic review to investigate the effects of VR-based interventions on end-of-life patients. METHODS AND ANALYSIS: This protocol for conducting a systematic review and meta-analysis will be prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. We will conduct a series of searches from inception to 31 July 2022 in the following databases: PubMed, Embase, Web of Science, the Cochrane Library, JBI, EBSCO, CNKI, Wanfang and SinoMed. The key concepts of 'virtual reality' and 'end-of-life' will be combined in each database using both free-text terms and controlled vocabulary terms (eg, MeSH/Emtree terms), if available. Two independent reviewers will use raw data to explore the effectiveness of VR for symptom management in end-of-life patients. The Cochrane Risk-of-Bias tool will be used to assess the risk of bias of included studies. Disagreements will be resolved by a third independent reviewer to reach a consensus. For the included articles, Review Manager software will be used for data synthesis and I2 statistics will be used to measure the heterogeneity. Subgroup analyses and sensitivity analyses will be used to identify the source of heterogeneity. ETHICS AND DISSEMINATION: As this is a protocol for a systematic review and meta-analysis, patients will not be included in this study. For this reason, ethical approval is not required. In order to disseminate the research findings, the results and conclusions of this review will be submitted to a worldwide journal. PROSPERO REGISTRATION NUMBER: CRD42022344679.

Anti-Na+/K+-ATPase DR antibody attenuates UUO-induced renal fibrosis through inhibition of Na+/K+-ATPase α1-dependent HMGB1 release.

Reduced Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of renal diseases. NKA-mediated Src activation is not the only reason for NKA-related renal fibrosis. In this study, we found that genetic reduction of NKAα1 exhibited exacerbated tubulointerstitial lesions and fibrosis in the UUO mice model. Activation of NKAα1 with an antibody against the extracellular DR region of the NKAα1 subunit (DRm217) prevented UUO-induced tubulointerstitial lesions, preserved kidney function, and decrease renal fibrosis. Further studies revealed that NKAα1 deficiency mice exhibited high inflammation factors expression when they suffered UUO surgery, compared with NKAα1+/+ (WT) mice. DRm217 alleviated inflammatory cell infiltration, suppress NF-κB phosphorylation, and decreased inflammatory factors expression in the UUO mice model. Released HMGB1 can trigger the inflammatory response and contribute to renal fibrosis. Knockdown of NKA in renal tubular cells or in NKAα1+/- mice was associated with more susceptibility to HMGB1 release in the UUO mice model. DRm217 exerted its antifibrotic effect via inhibiting HMGB1 release. Furthermore, AMPK activation participates in the effect of DRm217 on inhibiting HMGB1 release. Our findings suggest that NKAα1 is a regulator of renal fibrosis and its DR-region is a novel target on it.

Prenatal Lipopolysaccharide Exposure Alters Hepatic Drug-Metabolizing Enzyme Expression in Mouse Offspring via Histone Modifications.

Inflammation is a major regulator of drug-metabolizing enzymes (DMEs), therefore contributing to the interindividual variability of drug effects. However, whether prenatal inflammation affects DMEs expression in offspring remains obscure. This study investigated the effects of prenatal lipopolysaccharide (LPS) exposure on hepatic expression of inflammatory-related genes, nuclear receptors, and DMEs in offspring mice. Prenatal LPS exposure on gestational day (GD) 10 led to higher expression of NF-κB, Pxr, and Cyp2b10, while lower expression of Car, Ahr, Cyp3a11, and Ugt1a1 in postnatal day (PD) 30 offspring. However, multiple doses of LPS exposure on GD10-14 resulted in higher levels of inflammatory-related genes, Cyp1a2, and Cyp2b10, and lower levels of Pxr and Cyp3a11 in PD30 offspring liver. For PD60 offspring, decreased hepatic expression of NF-κB and IL-6, and increased expression of Pxr and Cyp3a11 were seen in single-dose LPS groups, whereas opposite results were observed in the multiple-dose LPS groups. Notably, enhanced H3K4me3 levels in the PXR response elements of the Cyp3a11 promoter were observed in the liver of PD60 offspring mice from dams treated with multiple doses of LPS during pregnancy. Overall, this study suggests that parental LPS exposure could persistently alter the hepatic expression of DMEs, and histone modifications may contribute to the long-term effects.

The prevalence and molecular epidemiology of vancomycin-resistant Enterococcus (VRE) carriage in patients admitted to intensive care units in Beijing, China.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) can be carried in the gut for a long period and its carriage status is associated with subsequent infections. This study aimed to investigate the frequency of intestinal VRE carriage in intensive care patients in Beijing. METHODS: A multicenter, retrospective cross-sectional study was conducted at six hospitals in Beijing, China. All patients admitted to intensive care units (ICUs) between April 2 and May 1, 2017, were enrolled, and their clinical data were gathered by reviewing electronic medical records. Rectal swabs collected from patients were stored at -80 °C in the Institute of Clinical Pharmacology, Peking University First Hospital, and they were selectively cultured for VRE, then the identified strains were analyzed by polymerase chain reaction (PCR) to detect the glycopeptide resistance gene and were characterized by multilocus sequence typing (MLST). RESULTS: Of 148 patients recruited, 46 (31.1%) carried VRE, with the majority (n = 42) being Enterococcus faecium. In total, 78.3% of the VRE were vanA positive and 15.2% vanM positive, while 6.5% undetected glycopeptide resistance gene. The predominant ST was ST78 (47.6%) followed by ST192 (14.3%), ST555 (9.5%), and ST789 (9.5%). Multivariate analysis showed that factors associated VRE carriage were patients aged >65 years (odds ratio [OR], 3.786; 95% confidence interval [CI], 1.402-10.222) and recent third-generation cephalosporins use (OR, 6.360; 95% CI, 1.873-21.601). CONCLUSIONS: The overall proportion of VRE carriage in patients admitted to ICUs was markedly high in Beijing, China. The vanM gene has been spread widely but vanA gene was the dominant resistance determinant in VRE in Beijing.

Diosgenin alleviates nonalcoholic steatohepatitis through affecting liver-gut circulation.

Nonalcoholic steatohepatitis (NASH), as the aggressive form of nonalcoholic fatty liver disease (NAFLD), rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NASH treatment. Diosgenin possesses multiple beneficial effects towards inhibition of lipid accumulation, cholesterol metabolism, fibrotic progression and inflammatory response. However, there has been no report concerning its effects on NASH so far. Using methionine and choline-deficient (MCD) feeding mice, we evaluated the anti-NASH effects of diosgenin. 16 S rDNA was used to investigate gut microbiota composition. Transcriptome sequencing, LC/MS and GC/MS analysis were used to evaluate bile acids (BAs) metabolism and their related pathway. Compared with the MCD group, diosgenin treatment improved the hepatic dysfunction, especially decreased the serum and hepatic TC, TG, ALT, AST and TBA to nearly 50%. Content of BAs, especially CA and TCA, were decreased from 59.30 and 26.00-39.71 and 11.48 ng/mg in liver and from 0.96 and 2.1-0.47 and 1.13 µg/mL in serum, and increased from 7.01 and 11.08-3.278 and 5.11 ng/mg in feces, respectively. Antibiotic and fecal microbiota transplantation (FMT) treatment further confirmed the therapeutic effect of diosgenin on gut microbiota, especially Clostridia (LDA score of 4.94), which regulated BAs metabolism through the hepatic FXR-SHP and intestinal FXR-FGF15 pathways. These data indicate that diosgenin prevents NASH by altering Clostridia and BAs metabolism. Our results shed light on the mechanisms of diosgenin in treating NASH, which pave way for the design of novel clinical therapeutic strategies.

Adherence to High Dietary Diversity and Incident Cognitive Impairment for the Oldest-Old: A Community-Based, Nationwide Cohort Study.

BACKGROUND AND AIMS: Dietary diversity change is associated with cognitive function, however, whether the effect still exists among the oldest-old (80+) is unclear. Our aim was to examine the effect of dietary diversity changes on cognitive impairment for the oldest-old in a large prospective cohort. METHODS: Within the Chinese Longitudinal Healthy Longevity Study, 6237 adults older than 80 years were included. The dietary diversity score (DDS) was assessed by a simplified food frequency questionnaire (FFQ). Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than 18 points. Cognitive decline was defined as a reduction of total MMSE score ≥3 points, and cognitive decline of different subdomains was defined as a reduction of ≥15% in the corresponding cognitive domain. The multivariate-adjusted Cox proportional hazard model evaluated the effects of DDS change on cognitive decline. The linear mixed-effect model was used to test subsequent changes in MMSE over the years. RESULTS: During 32,813 person-years of follow-up, 1829 participants developed cognitive impairment. Relative to the high-high DDS change pattern, participants in the low-low and high-low patterns were associated with an increased risk of cognitive impairment with a hazard ratio (95% confidential interval, CI) of 1.43 (1.25, 1.63) and 1.44 (1.24, 1.67), and a faster decline in the MMSE score over the follow-up year. Participants with the low-high pattern had a similar incidence of cognitive impairment with HRs (95% CI) of 1.03 (0.88, 1.20). Compared with the stable DDS status group (-1-1), the risk of cognitive impairment was higher for those with large declines in DDS (≤-5) and the HR was 1.70 (95% CI: 1.44, 2.01). CONCLUSIONS: Even for people older than 80, dietary diversity change is a simple method to identify those who had a high risk of cognitive decline. Keeping high dietary diversity is beneficial for cognitive function and its subdomain even in the final phase of life, especially for females and the illiterate oldest-old.

Self-Medication Behaviors of Chinese Residents and Consideration Related to Drug Prices and Medical Insurance Reimbursement When Self-Medicating: A Cross-Sectional Study.

BACKGROUND: Self-medication has become a common phenomenon. Economic factors are important factors that affect the self-medication of residents. This study aimed to investigate the current status of self-medication behaviors in China and explored the related factors affecting considerations associated with medical insurance reimbursement or drug price in self-medication. METHODS: A national cross-sectional investigation was conducted among Chinese people over 18 years old under a multi-stage sampling method through a questionnaire, which includes demographic sociological characteristics, self-medication behaviors and scales. The Chi-square test was used to analyze whether the respondents consider medical insurance reimbursement or drug price as an important factor when purchasing over-the-counter (OTC) drugs. Logistic regression was used to examine the associated factors of considering medical insurance reimbursement or drug price. RESULTS: In total, 9256 respondents were included in this study; 37.52% of the respondents regarded drug prices as an important consideration, and 28.53% of the respondents attached great importance to medical insurance reimbursement. Elderly respondents who lived in the central region, had medical insurance, and had lower levels of health literacy were more likely to consider the medical insurance reimbursement, while respondents with high monthly family income as well as students were less likely to consider the same issue (p < 0.05). Respondents settled in the central and western regions, students, those without fixed occupations, those who suffered from chronic diseases, or those with lower health literacy were more likely to consider drug prices, while the respondents with bachelor degrees, urban population and high per capita monthly income were less likely to consider the drug prices (p < 0.05). CONCLUSION: Self-medication behaviors with OTC drugs were prevalent in China, and consideration factors of medical insurance reimbursement or drug prices were related to socio-demographic characteristics and health literacy. There is a need to take measures to reduce the economic burden of self-medication, improve the health literacy of residents and strengthen public health education.

In vitro and in vivo activities of a novel ß-lactamase inhibitor combination imipenem/XNW4107 against recent clinical Gram-negative bacilli from China.

OBJECTIVES: XNW4107 is a novel ß-lactamase inhibitor that possesses broad activity against serine-ß-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107. METHODS: The minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy. RESULTS: MIC90 of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC90 of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC90 of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC90 of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 × MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo. CONCLUSIONS: The broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate.

Comprehensive molecular mechanisms and clinical therapy in nonalcoholic steatohepatitis: An overview and current perspectives.

Our understanding of nonalcoholic steatohepatitis (NASH) pathophysiology continues to advance rapidly. Given the complexity of the pathogenesis of NASH, the field has moved from describing the single pathogenesis of NASH to deeply phenotyping with a description of the multi-mechanism and multi-target pathogenesis that includes glucose, lipid and cholesterol metabolism, fibrotic progression, inflammation, immune reaction and apoptosis. To make the picture more complex, the pathogenesis of NASH involves pathological connections between the liver and several organs such as the adipose, pancreas, kidney and gut. Numerous pharmacologic candidates have been tested in clinical trials and have generated some positive results. Importantly, PPAR as triglyceride synthesis inhibitor and FXR as bile acids synthesis inhibitor have displayed beneficial effects on candidates for lipid and cholesterol metabolism. Although the efficacy of these drugs has been affirmed, serious side effects hinder their further development. It is a particularly important task to carry out the in-depth long-term research. Additionally, drug combination increases response rate and reduces side effects of a single drug. Mastering the advantages and limitations of clinical candidate drugs and continuous improvement and innovation are necessary to formulate a new strategy for the future treatment of NASH.

Antimicrobial Susceptibility Trends Among Gram-Negative Bacilli Causing Bloodstream Infections: Results from the China Antimicrobial Resistance Surveillance Trial (CARST) Program, 2011-2020.

Purpose: The antimicrobial resistance profiles of gram-negative bacilli causing bloodstream infections have changed over time, while comprehensive and real-time surveillance data are limited in China. This study aimed to review the antimicrobial susceptibility trends among main gram-negative bacilli isolated from blood specimens in China. Methods: From 2011 to 2020, a total of 4352 non-duplicate isolates were collected from 21 tertiary hospitals in 18 provinces or cities across China. Antimicrobial susceptibility testing was conducted by the agar dilution method recommended by the Clinical and Laboratory Standards Institute (CLSI), and the results were interpreted using CLSI criteria. Results: During this 10-year surveillance period, meropenem and imipenem were the most effective agents against Escherichia coli (resistance remaining <5%). The proportion of ESBL-producing isolates in carbapenem-susceptible E. coli displayed a decreasing trend (from 72.9% to 51.2%). The resistance rates of Klebsiella pneumoniae to meropenem and imipenem increased from 3.3% and 1.6% in the 2011-12 period to 15.0% and 15.4% in the 2019-20 period, respectively. Carbapenems and amikacin were the most active agents against Enterobacter cloacae. The resistance rates of Pseudomonas aeruginosa to meropenem and imipenem increased from 13.1% and 17.7% in the 2015-16 period to 24.5% and 21.0% in the 2019-20 period, respectively. Few agents showed activity against Acinetobacter baumannii. The frequency of imipenem-non-susceptible A. baumannii remained stable (remaining ~70%). Conclusion: The rapid spread of carbapenem-resistant K. pneumoniae has been serious in recent years. Conversely, the prevalence of ESBL-producing isolates was decreased. Carbapenems are still effective against gram-negative bacilli causing BSIs, except for A. baumannii. More attention should be given to A. baumannii, considering its high resistance against different classes of antimicrobials.

Q-marker identification of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. in pulmonary metastasis of liver cancer mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Paridis saponins (RPS) as the mainly active components of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz., possess tumor therapeutic potential. However, the anti-tumor material basis of RPS in liver cancer pulmonary metastasis remains poorly understood. The objective of this study was to identify the distribution and anti-cancer effects of RPS in liver cancer pulmonary metastatic model. MATERIALS AND METHODS: In this study, a mouse liver cancer pulmonary metastasis model was established to determine the distribution of different saponins in the tissues by UPLC-MS and plasma protein binding rate. RESULTS: As a result, RPS prolonged the survival time and inhibited the pulmonary metastasis in H22 injected mice through its underlying mechanism. UPLC-MS identified saponins from RPS such as PVII, PH, PVI, PII, gracillin and PI in tissues, which may be regarded as the Q-markers in RPS. Surprisingly, the concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. Besides, plasma protein binding rate of PII was higher than that of PVII. CONCLUSION: These findings suggested that PVII, PH, PVI, PI, PII and gracillin are regarded as the Q-markers of RPS in liver cancer pulmonary metastasis. The concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. It would be helpful for understanding the importance of RPS with anticancer activities in the future.

Effects of fructose from apple and honey on serum uric acid in young Chinese: Randomized crossover trials.

BACKGROUND AND OBJECTIVES: Overconsumption of drinks containing fructose increases the risk for hyperuricemia and gout. Comparative analysis evaluating the indicators of serum uric acid (SUA) load caused by natural food-derived fructose and pure fructose in sweeteners is lacking. We aimed to uncover the effect of fructose from apple and honey and pure fructose powder on the SUA concentration of healthy young Chinese individuals. METHODS AND STUDY DESIGN: Two randomized crossover trials were performed. The participants were randomly assigned to consume apple or honey (test food) or pure fructose powder (reference food); one week later, the groups' dietary intervention was switched. Blood samples were collected at 0, 30, 60, and 120 min after meal to measure the SUA and blood glucose concentrations. RESULTS: At 30 and 60 min, the SUA concentration in participants consuming apple or honey was lower than in those consuming fructose powder. At 120 min, the SUA concentration of participants consuming apple returned to baseline. The areas under the curve (AUC) within 2 h (2h- AUCs) of SUA exhibited the trend of fructose >honey >apple. The 2h-AUC ratio between test food and reference food was determined using the uric acid index to assess the efficiency of food-derived fructose in increasing the SUA concentration. The uric acid index of honey was higher than that of apple. Men had higher postprandial SUA concentration than women. CONCLUSIONS: Food-derived fructose caused a lighter load on uric acid metabolism than pure fructose. Uric acid index can be useful for distinguishing fructose-containing foods.