Influences of Propofol, Ciprofol and Remimazolam on Dreaming During Anesthesia for Gastrointestinal Endoscopy: A Randomized Double-Blind Parallel-Design Trial.

Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.

Remarkable adsorption of As(V) by Fe3+ and Mg2+ modified alginate porous beads (Fe/Mg-SA) via a facile method.

Although sodium alginate (SA) is frequently utilized because of its good gelling properties, the substance's dearth of adsorption active sites prevents it from effectively removing heavy metals. Herein, SA was used as the base material to form a cross-linked structure with Fe3+ and Mg2+, and gel beads with a diameter of 2.0 ± 0.1 mm with specific adsorption on As(V) were synthesized as adsorbent (Fe/Mg-SA). Fe/Mg-SA was systematically characterized, and its adsorption properties were investigated by varying several conditions. Fe/Mg-SA had a wide pH application range. The adsorption kinetics revealed that a quasi-secondary kinetic model was followed. The adsorption process is linked to the complexation of hydroxyl and AsO43-, chemisorption predominated the adsorption process. The maximal adsorption capacity of Fe/Mg-SA is determined by fitting the Langmuir model to be 37.4 mg/g. Compared to other adsorbents, it is simpler to synthesis, more effective and cheaper. Each treatment of 1 m3 wastewater of Fe/Mg-SA only costs ¥ 38.612. The novel gel beads synthesized provides a better option for purifying groundwater contaminated with As(V).

The identification of key metabolites and mechanisms during isoniazid/rifampicin-induced neurotoxicity and hepatotoxicity in a mouse model by HPLC-TOF/MS-based untargeted urine metabolomics.

The co-administration of isoniazid (INH) and rifampicin (RIF) is associated with hepatotoxicity and neurotoxicity. To systematically investigate the mechanisms of hepatotoxicity and neurotoxicity induced by INH/RIF, we used high performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics to analyze urine from a mouse model and screened a range of urinary biomarkers. Mice were orally co-administered with INH (120 mg/kg) and RIF (240 mg/kg) and urine samples were collected on days 0, 7, 14 and 21. Hepatotoxicity and neurotoxicity were assessed by samples of liver, brain and kidney tissue which were harvested for histological analysis. Toxicity analysis revealed that INH/RIF caused hepatotoxicity and neurotoxicity in a time-dependent manner; compared with day 0, the levels of 35, 82 and 86 urinary metabolites were significantly different on days 7, 14 and 21, respectively. Analysis showed that by day 21, exposure to INH+RIF had caused disruption in vitamin B6 metabolism; the biosynthesis of unsaturated fatty acids; tyrosine, taurine, hypotaurine metabolism; the synthesis of ubiquinone and other terpenoid-quinones; and the metabolism of tryptophan, nicotinate and nicotinamide. Nicotinic acid, nicotinuric acid and kynurenic acid were identified as sensitive urinary biomarkers that may be useful for the diagnosis and evaluation of toxicity.

Potential role of irisin in digestive system diseases.

Digestive system diseases (DSD) are very complex conditions that severely threaten human health. Therefore, there is an urgent need to develop new pharmacological treatment strategies. Irisin, a myokine discovered in 2012, is produced by fibronectin type III domain-containing protein 5 (FNDC5), which is a transmembrane protein. Irisin is involved in promoting the browning of white adipose tissue, the regulation of energy metabolism, and the improvement of insulin resistance. Irisin is also an essential mediator of the inflammatory response, oxidative stress, and cell apoptosis. Recent studies have proved that irisin concentration is altered in DSD and exerts pivotal effects on the initiation, progression, and prognosis of these diseases through various mechanisms. Therefore, studying the expression and function of irisin may have great significance for the diagnosis and treatment of DSD. Here, we focus on irisin and explore the multiple molecular pathways targeted by irisin therapy. This review indicates that irisin can serve as a diagnostic marker or potential therapeutic agent for DSD. DATA AVAILABILITY: Not applicable.

Involvement of the SIRT1-NLRP3 pathway in the inflammatory response.

The silent information regulator 2 homolog 1-NACHT, LRR and PYD domains-containing protein 3 (SIRT1-NLRP3) pathway has a crucial role in regulation of the inflammatory response, and is closely related to the occurrence and development of several inflammation-related diseases. NLRP3 is activated to produce the NLRP3 inflammasome, which leads to activation of caspase-1 and cleavage of pro-interleukin (IL)-1ß and pro-IL-18 to their active forms: IL-1ß and IL-18, respectively. They are proinflammatory cytokines which then cause an inflammatory response.SIRT1 can inhibit this inflammatory response through nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B pathways. This review article focuses mainly on how the SIRT1-NLRP3 pathway influences the inflammatory response and its relationship with melatonin, traumatic brain injury, neuroinflammation, depression, atherosclerosis, and liver damage. Video Abstract.

Single-cell microfluidics enabled dynamic evaluation of drug combinations on antibiotic resistance bacteria.

The rapid spread of antibiotic resistance has become a significant threat to global health, yet the development of new antibiotics is outpaced by emerging new resistance. To treat multidrug-resistant bacteria and prolong the lifetime of existing antibiotics, a productive strategy is to use combinations of antibiotics and/or adjuvants. However, evaluating drug combinations is primarily based on end-point checkerboard measurements, which provide limited information to study the mechanism of action and the discrepancies in the clinical outcomes. Here, single-cell microfluidics is used for rapid evaluation of the efficacy and mode of action of antibiotic combinations within 3 h. Focusing on multidrug-resistant Acinetobacter baumannii, the combination between berberine hydrochloride (BBH, as an adjuvant) and carbapenems (meropenem, MEM) or ß-lactam antibiotic is evaluated. Real-time tracking of individual cells to programmable delivered antibiotics reveals multiple phenotypes (i.e., susceptible, resistant, and persistent cells) with fidelity. Our study discovers that BBH facilitates the accumulation of antibiotics within cells, indicating synergistic effects (FICI = 0.5). For example, the combination of 256 mg/L BBH and 16 mg/L MEM has a similar killing effect (i.e., the inhibition rates >90%) as the MIC of MEM (64 mg/L). Importantly, the synergistic effect of a combination can diminish if the bacteria are pre-stressed with any single drug. Such information is vital for understanding the underlying mechanisms of combinational treatments. Overall, our platform provides a promising approach to evaluate the dynamic and heterogenous response of a bacterial population to antibiotics, which will facilitate new drug discovery and reduce emerging antibiotic resistance.

Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate.

Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome.

Integration of metabolomics and proteomics analysis to explore the mechanism of neurotoxicity induced by receipt of isoniazid and rifampicin in mice.

Isoniazid (INH) and rifampicin (RIF) are co-administered in tuberculosis treatment but can cause neurotoxicity, and the mechanism is not known. To explore this mechanism, we employed an integrated approach using metabolomics analysis (MA) and proteomics analysis (PA). Male mice were divided into three groups and administered vehicle (control group), or co-administered INH (120 mg/kg) and RIF (240 mg/kg), for 7 or 14 days. Mice brains were collected for mass spectrometry-based PA and MA plus lipidomics analysis. Measurement of brain levels of malondialdehyde and superoxide dismutase revealed time-dependent brain injury after exposure to INH+RIF for 7 and 14 days. Also, 422 proteins, 35 metabolites, and 21 lipids were dysregulated and identified. MA demonstrated "purine metabolism," "phenylalanine, tyrosine and tryptophan biosynthesis," "biosynthesis of unsaturated fatty acids," "phenylalanine metabolism," and "arginine biosynthesis" to be disturbed significantly. PA demonstrated pathways such as "lipids," "amino acids," and "energy metabolism" to be disrupted. Peroxisome proliferator-activated receptor (PPAR) pathways were changed in energy metabolism, which led to the neurotoxicity induced by INH+RIF. Immunohistochemical analyses of PPARs in mice brains verified that PPAR-α and -γ expression was downregulated. PPAR-α and -γ activation might be a key target for alleviating INH+RIF-induced neurotoxicity.

Exploration of the underlying mechanisms of isoniazid/rifampicin-induced liver injury in mice using an integrated proteomics and metabolomics approach.

The hepatotoxic mechanism resulting from coadministration of isoniazid (INH) and rifampicin (RIF) are complex and studies remain inconclusive. To systematically explore the underlying mechanisms, an integrated mass-based untargeted metabolomics and label-free quantitative proteomics approach was used to clarify the mechanism of INH/RIF-induced liver injury. Thirty male mice were randomly divided into three groups: control (receiving orally administered vehicle solution), INH (150 mg/kg) + RIF (300 mg/kg) orally administered for either 7 or 14 days, respectively. Serum was collected for the analysis of biochemical parameters and liver samples were obtained for mass spectrum-based proteomics, metabolomics, and lipidomics analysis. Overall, 511 proteins, 31 metabolites, and 23 lipids were dysregulated and identified, and disordered biological pathways were identified. The network of integrated multiomics showed that glucose, lipid, and amino acid metabolism as well as energy metabolism were mainly dysregulated and led to oxidative stress, inflammation, liver steatosis, and cell death induced by INH and RIF. Coadministration of INH and RIF can induce liver injury by oxidative stress, inflammation, liver steatosis, and cell death, and the reduction in glutathione levels may play a critical role in these systematic changes and warrants further study.

A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota.

Metabolic interactions within gut microbiota play a vital role in human health and disease. Targeting metabolically interacting bacteria could provide effective treatments; however, obtaining functional bacteria remains a significant challenge due to the complexity of gut microbiota. Here, we developed a facile droplet-based approach to isolate and enrich functional gut bacteria that could utilize metabolites from an engineered butyrate-producing bacteria (EBPB) of anti-obesity potential. This involves the high throughput formation of single-bacteria droplets, followed by culturing "droplets" on agar plates to form discrete single-cell colonies. This approach eliminates the need for sophisticated s instruments to sort droplets and thus allows the operation hosted in a traditional anaerobic chamber. In comparison to the traditional culture, the droplet-based approach obtained a community of substantially higher diversity and evenness. Using the conditioned plates containing metabolites from the EBPB supernatant, we obtained gut bacteria closely associated or interacting with the EBPB. These include anaerobic Lactobacillus and Bifidobacterium, which are often used as probiotics. The study illustrates the potential of our approach in the search for the associated bacteria within the gut microbiota and retrieving those yet-to-be cultured.

Let the Farmers Embrace "Carbon Neutrality": Taking the Centralized Biogas as an Example.

The promotion of rural centrally produced biogas (CPB) is an effective carbon neutrality development solution in rural areas. How to better encourage farmers to adopt such products is an important part of the sustainable development of a project. For this reason, focus is needed on the "willingness to embrace (WTE)" and "Willingness to motivate (WTM)" of rural residents for CPB projects and their influencing factors. We chose to conduct questionnaire surveys in rural areas of the Hebei and Shandong provinces of China, using the contingent valuation method (CVM). The results show that 85% of the respondents support CPB. Compared with urban gas, the subsidy demand of rural residents for CPB is 56.78%. The influencing factors of the residents' WTE are affected by the number of children in the family, whether the village cadres are installed in the family, solar water heaters installed in the family, knowledge and attitudes towards environmental protection, and the embracing of daily energy habits. The influencing factors on the residents' WTM are age, education level, ownership of arable land, knowledge of environmental protection, etc. Therefore, we propose policy recommendations. First, we must fully understand the willingness and demands of farmers, adopt a reasonable compensation response mechanism, and scientifically calculate financial inputs. The second step is to guide farmers through multi-channel publicity. Third, we aim to improve project operation efficiency, reduce operating costs, and minimize the government's financial burden on the basis of ensuring that farmers' demands are considered in a coordinated manner.

Understanding the Influence of Initial Values of College Students in Shaping Pro-Environmental Behavioral Intention.

Pro-environmental behaviors are rooted in values, and understanding the initial values among college students is pivotal in developing educational strategies to improve their pro-environmental behavior. However, most pro-environmental behavior studies fail to consider the social values and personal values as different dimensional or even conflicting values. This study integrated two distinct values, namely perceived social values and perceived personal values, with the technology acceptance model (TAM) to examine how different values shape college students' pro-environmental behavioral intentions. The proposed model was then empirically validated using survey data from 245 responses from freshmen students at a University in Chongqing. The findings reveal that while perceived social values and perceived personal values are both positively related to behavioral intention, the effect sizes of the former are much larger. Our findings highlight that higher institutions and instructors should continue shaping the prosocial values among college students and create personal values from pro-environmental behavior to reduce the detrimental impact on the environment and achieve sustainability.

Understanding the impact of emotional support on mental health resilience of the community in the social media in Covid-19 pandemic.

BACKGROUND: Emotional support in social media can act as a buffer against the negative impact of affective disorders. However, empirical evidence relating to emotional support in social media and how it influences the wider public remains scanty. The objective of this study is therefore to conduct a prototype investigation into the translation mechanism of emotional support in social media, providing empirical evidence for practitioners to use to tackle mental health issues for the wider public. METHODS: A regression model is proposed to examine the relationship between perceived and received emotional support. Received emotional support is set as the dependent variable and measured using public activity. Perceived emotional support is derived using Natural Language Processing (NLP)-based content analysis. The model is then analyzed using a panel date with a total number of 61,297 posts from 17 Weibo accounts in 17 provincial administrative units in China. RESULTS: The relationship between perceived and received emotional support is not linear but complex, suggesting that translation of emotional support is not automatic. Further, our empirical evidence suggests that the translation of emotional support in social media is affected by frequency and pandemic stage. LIMITATIONS: The study does not examine the direct relationship between perceived and received emotional support, instead adopting public activity as a proxy for the latter construct. In addition, the relationship between perceived and received emotional support is more complex than linear, requiring further model and theory development.

Untargeted metabolomics analysis of omeprazole-enhanced chemosensitivity to cisplatin in mice with non-small cell lung cancer.

Drug resistance of tumors remains a major barrier in cisplatin (CDDP)-based chemotherapy. Omeprazole (OME) is often utilized during chemotherapy to alleviate gastrointestinal symptoms. In a previous investigation, we demonstrated a protective effect of OME against CDDP-induced kidney injury. To further establish whether OME could enhance chemosensitivity to CDDP and the underlying mechanisms, an in vivo tumor-bearing mouse model with CDDP-resistant A549 non-small cell lung cancer (A549/CDDP) was established in the current study. A high-performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics approach for tumor tissue and serum was employed to explore the mechanisms underlying the enhanced therapeutic effects of co-administration of CDDP and OME. Notably, tumor weights of mice in the CDDP + OME group were significantly decreased compared with those treated with CDDP alone. HE and TUNEL staining revealed more significant apoptosis of tumor cells in the group co-administered CDDP + OME relative to CDDP alone. Overexpression of multidrug resistance-associated protein 2 in CDDP-resistant tumors was significantly reversed upon treatment with CDDP + OME. PCA score plots of the groups co-treated with CDDP + OME were clearly separated from those treated with CDDP alone in metabolomics analysis for tumor and serum samples, clearly suggesting that co-administration of OME enhances the antitumor effect of CDDP. Subsequently, 10 and 7 metabolites in CDDP + OME group with significant changes in tumor and serum compared with CDDP group, respectively, were identified. Pathway analysis both in tumor and serum samples revealed regulation of the metabolism of purines, several amino acids and riboflavin in enhanced chemotherapy with both OME and CDDP. The collective findings provide beneficial novel insights into drug-drug interactions, which could improve the application of CDDP in clinical practice.

Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review.

BACKGROUND: Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD). METHODS: PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021. RESULTS: Ten studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events. CONCLUSIONS: According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.

Uptake of arsenic(V) using iron and magnesium functionalized highly ordered mesoporous MCM-41 (Fe/Mg-MCM-41) as an effective adsorbent.

Mesoporous silica (MCM-41) is widely used as a supporting material due to its large specific surface area and good stability, but it cannot remove heavy metals due to the lack of adsorption active sites. In this study, the MCM-41 (a mesoporous SiO2 material) decorated with iron and magnesium oxide (Fe/Mg-MCM-41) was found to be an excellent adsorbent to remove arsenic(V) from water. FTIR, BET, TEM-EDS, XRD, XPS, etc. were applied for characterization analysis. Adsorption isotherms were fitted well by the Langmuir model and the experimental maximum adsorption capacity of Fe/Mg4-MCM-41 (magnesium accounts for 4%) was 71.53 mg/g at pH = 3. Thermodynamics analysis suggested exothermic nature of adsorption behavior. Kinetic process was well described by the pseudo-second-order model and adsorption rate was controlled by intraparticle diffusion and film diffusion. Moreover, the adsorption behavior of As(V) onto Fe/Mg4-MCM-41 was investigated under different reaction conditions, such as pH, temperature, Mg-doping and competing ions. The results showed that loading a certain amount of magnesium can significantly improve arsenic removal efficiency. Additionally, Fe/Mg4-MCM-41 exhibits high arsenic(V) removal in the wide pH range of 3-10. The Fe/Mg4-MCM-41 can be regenerated and used after four consecutive cycles. The high arsenic(V) sorption capacity, wide range of pH applications, ability to regenerate, and reusability of Fe/Mg4-MCM-41 confirmed that this adsorbent is promising for treating As-contaminated wastewater.

Risk factors for Clostridioides difficile infection in children and adolescents with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Risk factors and consequences associated with Clostridioides difficile infection (CDI) in children and adolescents with inflammatory bowel disease (IBD) are still uncertain. We conduct a systematic review and meta-analysis to assess risk factors and outcomes associated with CDI in children and adolescents with IBD. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from inception to 24th February, 2021. Studies investigating risk factors, bowel surgery rate in pediatric IBD patients with and without CDI were included. Random-effects model was used for calculating summary estimates. Newcastle-Ottawa scale (NOS) was used for quality assessment. RESULTS: Fourteen studies, comprising 17,114 patients, were included. There was a significant association between 5-aminosalicylic acid (5-ASA) use and CDI [odds ratio (OR) = 1.95, 95% confidence interval (CI) 1.26-3.03], with minimal heterogeneity (I2 = 0.00%). Increased risk of active disease (OR = 4.66, 95% CI 2.16-10.07) were associated with CDI in those studies performed in high quality score (NOS > 6) and significantly higher CDI rates in studies conducted outside USA (OR = 2.94, 95% CI 1.57-5.58). The bowel surgery rate in IBD with CDI was 3.8-57.1%, compared to that in IBD without CDI (0-21.3%). All studies were of moderate to high quality. CONCLUSIONS: 5-ASA use and active disease might be risk factors associated with CDI in children and adolescents with IBD. Bowel surgery rates associated with CDI in IBD patients varied greatly. Large-scale clinical studies on CDI in children and adolescents with IBD are still needed to verify risk factors and outcomes.

Polypharmacy and potentially inappropriate medications among elderly patients in the geriatric department at a single-center in China: A retrospective cross-sectional study.

ABSTRACT: The aging of the population has become a worldwide concern, especially in China. Polypharmacy and potentially inappropriate medications (PIMs) are prominent issues in elderly patients. Therefore, the aim of this study was to investigate the prevalence of polypharmacy and PIMs in older inpatients and further to explore the factors associated with PIM use.A retrospective, single-center, cross-sectional study was conducted. A total of 1200 inpatients aged 65 years or older admitted from January 2015 to December 2015 were included. The prevalence of polypharmacy (5-9 medications) and hyperpolypharmacy (10 or more medications) was calculated. The 2019 American Geriatric Society Beers criteria were applied to assess PIMs use. Multivariate logistic regression was used to determine the independent factors of PIM use, while zero-inflated negative binomial regression was performed to evaluate the relationship between polypharmacy and PIM use.The median age of the study population was 76 years (interquartile range = 71-81). The median number of medications was 9 (interquartile range = 7-12). 91.58% of the patients took 5 or more medications simultaneously, and 30.08% of the patients were subjected to one or more PIMs. Spironolactone, furosemide, and zopiclone were the top 3 most frequently encountered PIMs. Hyperpolypharmacy and older age were identified as independent factors associated with PIM use. The risk of PIMs rises with the number of medications prescribed.Polypharmacy and PIM use were common in our study, and the risk of PIM use correlated with an increase in the number of medications already prescribed.

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation.

CONTEXT: Severe nephrotoxicity greatly limits the clinical use of the common effective chemotherapeutic agent cyclophosphamide (CYP). Huaiqihuang (HQH) is a Chinese herbal complex with various pharmacological activities, widely used for treating kidney disease. OBJECTIVE: This study estimates the protective effect of HQH against CYP-induced nephrotoxicity in rats. MATERIALS AND METHODS: Four groups of 10 Sprague-Dawley rats were pre-treated with once-daily oral gavage of 3 and 6 mg/kg HQH for 5 days before receiving a single dose of CYP (200 mg/kg i.p.) on the 5th day; the control group received equivalent dose of saline. Renal function indices, morphological changes, oxidative stress, apoptosis and inflammatory mediators were measured. In addition, phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were analysed. RESULTS: Both doses of HQH reduced the levels of serum creatinine (31.27%, 43.61%), urea nitrogen (22.66%, 32.27%) and urine protein (12.87%, 15.98%) in the CYP-treated rats, and improved histopathological aberrations. Additionally, HQH decreased the production of MDA (37.02%, 46.18%) and increased the activities of antioxidant enzyme CAT (59.18%, 112.25%) and SOD (67.10%, 308.34%) after CYP treatment. HQH protected against CYP-induced nephrotoxicity by modulating apoptosis-related protein and suppressing the inflammatory responses. Furthermore, the phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were significantly boosted in CYP-treated rats, which was also abrogated by HQH treatment. CONCLUSIONS: HQH effectively protected against CYP-induced nephrotoxicity, which was associated with regulating oxidative stress, apoptosis and inflammation, and so HQH may be a useful agent for treating nephrotoxicity caused by CYP.

Questionnaire and Lactic Acid Sting Test Play Different Role on the Assessment of Sensitive Skin: A Cross-sectional Study.

BACKGROUND: Questionnaires and lactic acid sting test (LAST) are two widely used methods to identify sensitive skin. However, the self-perceived sensitive skin by questionnaires was not consistent with the determination of LAST. OBJECTIVE: The aim of the study was to measure the biophysical properties noninvasively of sensitive skin evaluated by questionnaire and LAST and to investigate their correlations with the scores of questionnaire and LAST. METHODS: A total of 209 healthy Chinese females completed the study. Self-assessment questionnaire and LAST were both performed to identify sensitive skin. Epidermal biophysical properties, including skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), a* value, L* value, skin elasticity, and skin pH, were measured with noninvasive instruments. RESULTS: The frequency of sensitive skin was 50.2% and 66.0% by questionnaire and LAST, respectively. Subjects with self-assessed sensitive skin had a slightly higher LAST positive rate. Skin hydration, sebum content, a* and EI values were significantly higher in the self-assessed sensitive skin group, while TEWL, a* and EI values increased but L* value decreased with significance in the LAST positive group. The LAST stingers among sensitive skin subjects had higher EI but not in the healthy skin subjects. In addition, questionnaire scores positively correlated with skin hydration, sebum content, a* and EI values, while a positive relationship of LAST scores with TEWL, a* and EI values was observed. The scores of questionnaire and LAST both negatively related to L* value. CONCLUSION: Self-assessed questionnaire is associated with sensitive skin featured by oily and red face without impaired barrier function, whereas LAST is suitable to identify fragile skin barrier and enhanced blood flow on the face. Combination of both methods to diagnose sensitive skin might be more reliable.