Depression and anxiety between nurses and nursing assistants working in long-term care facilities during the COVID-19 pandemic.

AIM: This study investigated the levels of depression and anxiety in nurses and nursing assistants working in long-term care facilities during the COVID-19 pandemic. We also explored the potential causes of depression and anxiety in nurses and nursing assistants working in long-term care facilities during the pandemic. BACKGROUND: The COVID-19 pandemic has had a considerable impact on long-term care facilities. The high infection and mortality rates for COVID-19 have resulted in an increased workload for caregivers. INTRODUCTION: The COVID-19 pandemic exposed caregivers working in long-term care facilities to higher risks of anxiety and depression. Additionally, the high risk of infection in the work environment and concerns about spreading COVID-19 to family members and long-term care facility residents led to various forms of stress among caregivers. METHODS: The present study was a cross-sectional study. Questionnaires were used to investigate depression and anxiety among regarding nurses and nursing assistants working in long-term care facilities during the pandemic. RESULTS: The depression and anxiety levels of the nurses were higher than nursing assistants, but had no statistically significant difference (p = 0.551). The factors influencing levels of depression and anxiety in nurses contained facility affiliation and experience working. In terms of nursing assistants, age, marital status, and facility affiliation were correlated with the levels of depression and anxiety. DISCUSSION: The pandemic has severely impacted caregivers. In the process of implementing pandemic prevention measures and providing care for COVID-19 patients, safeguarding the psychological health of caregivers is also essential. CONCLUSION: The levels of depression and anxiety in nurses were higher than in nursing assistants working in long-term care facilities during the pandemic. IMPLICATION FOR NURSING AND HEALTH POLICY: Long-term care facilities managers are recommended to enhance the education and training process for caregivers. Managers are also recommended to ensure provision of sufficient amounts of pandemic prevention equipment and resources.

Acute Pancreatitis in Pregnancy: A Propensity Score Matching Analysis and Dynamic Nomogram for Risk Assessment.

BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.

Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis.

BACKGROUND: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. RESULTS: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. CONCLUSIONS: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

Preparation of a ß-cyclodextrin grafted magnetic biochar for efficient extraction of four antiepileptic drugs in plasma samples.

Simultaneous monitoring of plasma concentration levels of multiple antiepileptic drugs (AEDs) is essential for dose adjustment in comprehensive epilepsy treatment, necessitating a sensitive technique for accurate extraction and determination of AEDs. Herein, a magnetic solid-phase extraction (MSPE) technique on the basis of modified biochar (BC) is investigated to extract four AEDs from plasma, in conjunction with high performance liquid chromatography. BC derived from Zizyphus jujuba seed shells was activated by phosphoric acid (PBC) and magnetized via coprecipitation to produce MPBC. The MPBCCD obtained after modification with ß-cyclodextrin (CD) was characterized and evaluated for adsorption. It exhibited fast adsorption kinetics based on second-order kinetics and satisfactory adsorption capacity for AEDs. Then it was employed as the MSPE adsorbent and the influencing parameters were optimized. The enrichment factor was 18.75. The validation analysis revealed a favorable linearity that ranged from 0.04 to 20 µg·mL-1 along with a low limit of detection of 6.85 to 10.19 ng·mL-1. The recovery of the AEDs ranged from 78.7 to 109.2 %, with relative standard deviations below 6.7 %. Using quantum chemistry theory calculations and experimental results analysis, the adsorption mechanism was investigated. It disclosed that the suggested strategy built upon MPBCCD was appropriate for the assessment of AEDs in plasma and expanded the usage of BC as the environmentally favorable matrix for the analysis of biological samples.

[Water-soluble Inorganic Ion Content of PM2.5 and Its Change Characteristics in Urban Area of Beijing in 2022].

To explore the content and variation characteristics of water-soluble ions of atmospheric fine particles (PM2.5) in a Beijing urban area and put forward the pollution prevention and control scheme, the water-soluble ions, gaseous precursors (SO2, NO2), and meteorological factors (temperature, RH) of PM2.5 in 2022 were analyzed and determined. The results showed that the water-soluble ions with the highest proportion in PM2.5 in the Beijing City urban area were NO3-, NH4+, and SO42-, accounting for 52.7% of PM2.5. The mass concentrations of PM2.5 and SNA were lower than the historical results, whereas the proportion of SNA, SOR, and NOR was higher than the historical results. This showed that the fine particulate matter pollution in Beijing has been significantly improved, but it still has strong secondary pollution characteristics. NO3-/SO42-(2.2) was higher than those of historical and nearby provinces and cities, reflecting the expanding influence of mobile sources. In terms of seasonal variation, PM2.5 showed the characteristic of high in autumn and low in summer. The proportion of NO3- was the highest in autumn, spring, and winter; the proportion of SO42- was the highest in summer; and the proportion of NH4+ changed little in each season. The seasonal variation rules of NOR and SOR were almost opposite, which reflected the difference in transformation factors between NOR and SOR. The main forms of SNA in the Beijing urban area were NH4NO3 and (NH4)2SO4. The neutralization degree of cations and anions was the highest in winter, the cation NH4+ was slightly insufficient in summer, and NH4+ was in excess in spring and autumn. The Beijing urban area was an ammonia-rich environment. In terms of pollution level, RH, particulate matter moisture, and water-soluble ions mass concentration all increased with the increase in pollution level, and SNA increased fastest, with its proportion in PM2.5 increasing first and then stabilizing, whereas the contribution rate of other water-soluble ions decreased gradually. In terms of spatial distribution, the mass concentration relationship of SNA at the central urban area and suburbs was NO3- > SO42- > NH4+, which reflected the pollution characteristics dominated by NO3-. The highest contribution rate of SNA to PM2.5 occurred in the eastern region, the central urban area, and the transmission point, indicating that the secondary reaction was relatively active in the central urban area and the eastern region, and the regional transport was also an important source of secondary ions.

[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis: A case report.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients. There is no consensus on how to treat S. typhimurium-triggered sHLH. CASE SUMMARY: A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S. typhimurium, human rhinovirus, and Mycoplasma pneumoniae infections. At the time of admission to our institution, the patient's T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6 (IL-6), 9.1 pg/mL for IL-10, and 246.7 pg/mL for interferon-gamma (IFN-γ), for which the ratio of IL-10 to IFN-γ was 0.04. In this study, the patient received meropenem, linezolid, and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy (10 mg/kg/d for 3 d) and antishock supportive treatment twice. After careful evaluation, this patient did not receive HLH chemotherapy and recovered well. CONCLUSION: S. Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ ≤ 1.33, an IL-10 concentration ≤ 10.0 pg/mL, and/or an IFN-γ concentration ≤ 225 pg/mL at admission. Early antimicrobial and supportive treatment was sufficient, and the HLH-94/2004 protocol was not necessary under these conditions.

Exploring the anti-skin inflammation substances and mechanism of Paeonia lactiflora Pall. Flower via network pharmacology-HPLC integration.

BACKGROUND: Paeonia lactiflora Pall. (PL) is widely used in China as a homologous plant of medicine and food. PL flower is rich in bioactive substances with anti-inflammatory effects, while the pathogenesis of skin inflammation is complex and the specific mechanism is not clear, the current treatment of skin inflammation is mainly hormonal drugs, and hormonal drugs have obvious toxic side effects. The research on the treatment of skin inflammation by PL flowers is relatively small, so this study provides a basis for the development and utilisation of PL resources. OBJECTIVE: Our study was to investigate the interventional effects of PL flower extracts on skin inflammation and thus to understand its functional role in the treatment of skin inflammation and its molecular mechanisms. METHODS: The major active substances in PL flower extracts were investigated by the HPLC-DAD method, and the potential targets of action were predicted by network pharmacology, which was combined with in vitro experimental validation to explore the mechanism of PL flower extracts on the regulation of skin inflammation. The HPLC-DAD analysis identified seven major active components in PL flower extracts, and in response to the results, combined with the potential mechanism of network pharmacological prediction with skin inflammation, the PL flower extract is closely related to MAPK and NF-κB signaling pathways. In addition, we also investigated the interventional effects of PL flower extract on skin inflammation by western blot detection of MAPK signaling pathway and NF-κB signaling pathway proteins in cells. RESULT: Seven active components were identified and quantified from the extract of PL flowers, including Gallic acid, 1,2,3,4,6-O-Pentagalloylglucose, Oxypaeoniflorin, Paeoniflorin, Albiflorin, Benzoyloxypeoniflorin, and Rutin. It was predicted targets for the treatment of skin inflammation, with PPI showing associations with targets such as TNF, MAPK1, and IL-2. KEGG enrichment analysis revealed that the main signaling pathways involved included MAPK and T cell receptor signaling pathways. Cell experiments showed that the peony flower extract could inhibit the release of NO and inflammatory factors, as well as reduce ROS levels and inhibit cell apoptosis. Furthermore, the extract was found to inhibit the activation of the MAPK and NF-κB signaling pathways in cells. CONCLUSIONS: In this study, we found that PL flower extract can inhibit the production of cell inflammatory substances, suppress the release of inflammatory factors, and deactivate inflammatory signaling pathways, further inhibiting the production of cell inflammation. This indicates that PL flower extract has a therapeutic effect on skin inflammation.

Detection of trace components in Xiangdan injection of Dalbergia odorifera based on microextraction and back-extraction along with bar-form-diagram strategy.

Xiangdan Injection are commonly used traditional Chinese medicine formulations for the clinical treatment of cardiovascular diseases. However, the trace components of Dalbergia odorifera in Xiangdan Injection pose a challenge for evaluating its quality due to the difficulty of detection. This study proposes a technology combining dispersive liquid-liquid microextraction and back-extraction (DLLME-BE) along with Bar-Form-Diagram (BFD) to address this issue. The proposed combination method involves vortex-mixing tetradecane, which has a lower density than water, with the sample solution to facilitate the transfer of the target components. Subsequently, a new vortex-assisted liquid-liquid extraction step is performed to enrich the components of Dalbergia odorifera in acetonitrile. The sample analysis was performed on HPLC-DAD, and a clear overview of the chemical composition was obtained by integrating spectral and chromatographic information using BFD. The combination of BFD and CRITIC-TOPSIS strategies was used to optimize the process parameters of DLLME-BE. The determined optimal sample pre-treatment process parameters were as follows: 200 µL extraction solvent, 60 s extraction time, 50 µL back-extraction solvent, and 90 s back-extraction time. Based on the above strategy, a total of 29 trace components, including trans-nerolidol, were detected in the Xiangdan Injection. This combination technology provides valuable guidance for the enrichment analysis of trace components in traditional Chinese medicines.

Explore the effect of pressure and time of compression on the risk of intraoperatively acquired pressure injury based on theoretical framework: A prospective study.

Surgery is a high risk factor for the occurrence of pressure injury (PI). On the basis of theoretical research, pressure and duration of pressure are key factors affecting PI. Pressure is affected by the individual pressure redistribution capacity. So our study aims to explore how the surgery time and pressure intensity affect the occurrence of PI and what are the risk factors. A prospective study. A total of 250 patients who underwent elective surgery in a grade-A general hospital from November 2021 to February 2023 were selected and divided into a group of 77 patients with IAPI (intraoperatively acquired pressure injury) and a group of 173 patients with no IAPI. Visual pressure inductive feedback system and body composition analysis technology were used to record the local pressure value and change of patients before and after anaesthesia. Relevant data of the patients were collected to explore the influencing factors. The maximum pressure and average pressure at the pressure site of the same patient changed before and after anaesthesia, and the pressure after anaesthesia was significantly higher than that before anaesthesia. There was no statistical difference in the average pressure after anaesthesia (p > 0.05), but the maximum pressure in the IAPI group was higher than that in the non-occurrence group (p < 0.05). The average pressure multiplied by the operation time in IAPI group is significantly higher than that in the non-IAPI group (p < 0.01). Multiple linear regression analysis (stepwise regression) showed that fat-free weight, age, waist circumference, body mass index (BMI) and gender were taken as independent variables into the regression model, affecting the maximum pressure. In addition, operation time ≥4 h may be a high risk factor for IAPI. In future studies, more objective research tools can be applied to improve the accuracy of predicting the risk of IAPI. In addition to gender and BMI, follow-up studies may consider including measures such as waist circumference and fat-free body weight in IAPI risk assessment to guide the clinical nursing work more scientifically.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

Patient-Controlled Subcutaneous Analgesia with Hydromorphone versus Oral Oxycontin for Opioid Titration of Cancer Pain: A Prospective Multicenter Randomized Trial.

Background: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain. Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5-11.5] hours vs.16.0 [95% CI:11.5-22.5] hours; p<0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0-3.5) than in the oxycontin group.(3.0; 2.5-4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5-3.0) vs 4.5;3.0-6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32). Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p<0.001), without significantly increasing adverse events (p=0.32).

Root rot of spinach caused by Pythium myriotylum and P. aphanidermatum in Taiwan.

Spinach (Spinacia oleracea) is a commonly used green vegetable. During September and October in both 2022 and 2023, a vegetable nursery company located among paddy rice fields in Taichung City, Taiwan, reported significant failures in spinach seedling production in net-houses with mean outdoor temperatures of 28.7℃. Abnormal growth was observed in approximately 30% of the spinach seedlings in each batch (n = 2,000 to 3,000), with aboveground tissues showing stunting, yellowing, and wilt, and underground tissues displaying root rot. The symptoms resembled the spinach damping-off documented in Taiwan in extension articles but which lacked complete pathogen identification. A total of 110 plants from two batches were used for pathogen isolation by placing roots on water agar incubated at 25℃ or were examined for the presence of oospores in diseased roots. Eighty-one percent of these plants were associated with Pythium. Nine Pythium isolates were used in subsequent analyses. Genomic DNA from these isolates was subjected to amplification of ITS, ß-tubulin gene (TUB2), and cytochrome C oxidase subunit Ⅱ (COXII) gene with primer pairs ITS1 / ITS4, BT5 / BT6, and FM58 / FM66 (Villa et al. 2006). Sequences of ITS (PP209187-PP209195), TUB2 (PP212864-PP212872), and COXII (PP212855-PP212863) were deposited in GenBank. Four isolates (sp01, sp02, sp03, and sp04) were 100% identical to the neotype strain (CBS 118.80) of Pythium aphanidermatum (Edson) Fitzp. for the ITS (761 bp), TUB2 (583 bp), and COXII (547 bp). Five isolates (2sp, 3sp, ND2-4sp, D3-4sp, and ND3-3sp) were 99.87%, 100%, and 99% identical to the reference strain (CBS 254.70) of Pythium myriotylum Drechsler for the ITS (762 bp), TUB2 (602 bp), and COXII (556 bp), respectively. Phylogenetic analysis of Pythium isolates inferred from concatenated sequences of the three genes (LéVesque and De Cock 2004; Villa et al. 2006) revealed that the same four isolates grouped with the neotype strain of P. aphanidermatum, and the five isolates clustered with the reference strain of P. myriotylum, each with a 100% bootstrap support. Morphological features of isolates ND3-3sp and sp01 were used for identification. Isolate ND3-3sp produced inflated lobulate sporangia and aplerotic and smooth oospores (16.3 to 25.1 um; n = 30) attached with three to five antheridia, consistent with identification as P. myriotylum. Isolate sp01 produced inflated lobulate sporangia and aplerotic and smooth oospores (17.0 to 24.0 um; n= 30) attached with a single intercalary antheridium, agreeing with the morphology of P. aphanidermatum (Van der Plaats-Niterink 1981). To investigate the pathogenicity of the nine Pythium isolates on spinach, 20 mycelial agar discs (4 mm in diameter) from a 2-day-old V8 culture of each isolate were used to induce sporangia and zoospores in 20 ml sterilized water at 25℃ with a 12 h light / dark regime. A 1.5 ml zoospore suspension (6 × 103 zoospores / ml) was dropped into BVB growth substrate of two spinach seedlings in 2-week-old at 25℃ with 12 h light / dark regime, resulting in symptoms resembling those observed in commercial nurseries at 7 days post-inoculation (dpi). Each Pythium isolate inoculated 20 seedlings in 10 cells of a planting tray. At 14 dpi, disease incidences were 95 to 100% for P. myriotylum isolates and 60 to 85% for P. aphanidermatum isolates, while control plants treated with water showed no symptoms. Re-isolated pathogens from the inoculated plants were morphologically identical to the inoculated isolates, completing Koch's postulates. Results of the pathogenicity assay, along with molecular and morphological identification, conclude that the root rot of spinach was caused by P. myriotylum and P. aphanidermatum. The two oomycetes were not formally documented to cause spinach diseases in Taiwan. Although P. myriotylum has been isolated from spinach (Wang et al. 2003), its pathogenicity to spinach was not documented worldwide. Root rot of spinach caused by P. aphanidermatum has been reported in the United States (Bates and Stanghellini 1984), Korea (Cho and Shin 2004), and Italy (Garibaldi et al. 2015). These pathogens thrive in humid and hot weather (Littrell and McCarter, 1970). Producing spinach in cooler weather or in a temperature-controlled environment may help prevent severe occurrence of the disease.

Synthesis and Characterisation of Hemihydrate Gypsum-Polyacrylamide Composite: A Novel Inorganic/Organic Cementitious Material.

This study combined inorganic α-hemihydrate gypsum (α-HHG) with organic polyacrylamide (PAM) hydrogel to create a novel α-HHG/PAM composite material. Through this facile composite strategy, this fabricated material exhibited a significantly longer initial setting time and higher mechanical strength compared to α-HHG. The effects of the addition amount and the concentration of PAM precursor solution on the flowability of the α-HHG/PAM composite material slurry, initial setting time, and mechanical properties of the hardened specimens were investigated. The structural characteristics of the composite material were examined using XRD, FE-SEM, and TGA. The results showed that the initial setting time of the α-HHG/PAM composite material was 25.7 min, which is an extension of 127.43% compared to that of α-HHG. The flexural strength and compressive strength of the oven-dried specimens were 23.4 MPa and 58.6 MPa, respectively, representing increases of 34.73% and 84.86% over values for α-HHG. The XRD, FE-SEM, and TGA results all indicated that the hydration of α-HHG in the composite material was incomplete. The incompleteness is caused by the competition between the hydration process of inorganic α-HHG and the gelation process of the acrylamide molecules for water, which hinders some α-HHG from entirely reacting with water. The enhanced mechanical strength of the α-HHG/PAM composite material results from the tight interweaving and integrating of organic and inorganic networks. This study provides a concise and efficient approach to the modification research of hemihydrate gypsum.

Whole-genome sequencing of Sphingobium baderi SC-1 and identification of a crucial 3-phenoxybenzoic acid-degrading gene.

As an efficient degradation strain, Sphingobium baderi SC-1 can breakdown 3-phenoxybenzoic acid (3-PBA) with high proficiency. To investigate the internal factors that regulate this process, we conducted whole-genome sequencing and successfully identified the pivotal 3-PBA-degrading gene sca (1,230 bp). After sca was expressed in engineered bacteria, a remarkable degradation efficiency was observed, as 20 mg/L 3-PBA was almost completely decomposed within 24 h. The phenol was formed as one of the degradation products. Notably, in addition to their ability to degrade 3-PBA, the resting cells proficiently degraded 4'-HO-3-PBA and 3'-HO-4-PBA. In conclusion, we successfully identified and validated sca as the pivotal enzyme responsible for the efficient degradation of 3-PBA from Sphingomonas baderi, providing a crucial theoretical foundation for further explorations on the degradation potential of SC-1.

Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.

A metabolomics study on carcinogenesis of ground-glass nodules.

Objective: This study aimed to identify differential metabolites and key metabolic pathways between lung adenocarcinoma (LUAD) tissues and normal lung (NL) tissues using metabolomics techniques, to discover potential biomarkers for the early diagnosis of lung cancer. Material and Methods: Forty-five patients with primary ground-glass nodules (GGN) identified on computed tomography imaging and who were willing to undergo surgery at Shanghai General Hospital from December 2021 to December 2022 were recruited to the study. All participants underwent video thoracoscopy surgery with segmental or wedge resection of the lung. Tissue samples for pathological examination were collected from the site of ground-glass nodules (GGN) lesion and 3 cm away from the lesion (NL). The pathology results were 35 lung adenocarcinoma (LUAD) cases (13 invasive adenocarcinoma, 14 minimally invasive adenocarcinoma, and eight adenocarcinoma in situ), 10 benign samples, and 45 NL tissues. For the untargeted metabolomics technique, 25 LUAD samples were assigned as the case group and 30 NL tissues as the control group. For the targeted metabolomics technique, ten LUAD samples were assigned as the case group and 15 NL tissues as the control group. Samples were analyzed by untargeted and targeted metabolomics, with liquid chromatography-tandem mass spectrometry detection used as part of the experimental procedure. Results: Untargeted metabolomics revealed 164 differential metabolites between the case and control groups, comprising 110 up regulations and 54 down regulations. The main metabolic differences found by the untargeted method were organic acids and their derivatives. Targeted metabolomics revealed 77 differential metabolites between the case and control groups, comprising 69 up regulations and eight down regulations. The main metabolic changes found by the targeted method were fatty acids, amino acids, and organic acids. The levels of organic acids such as lactic acid, fumaric acid, and malic acid were significantly increased in LUAD tissue compared to NL. Specifically, an increased level of L-lactic acid was found by both untargeted (variable importance in projection [VIP] = 1.332, fold-change [FC] = 1.678, q = 0.000) and targeted metabolomics (VIP = 1.240, FC = 1.451, q = 0.043). Targeted metabolomics also revealed increased levels of fumaric acid (VIP = 1.481, FC = 1.764, q = 0.106) and L-malic acid (VIP = 1.376, FC = 1.562, q = 0.012). Most of the 20 differential fatty acids identified were downregulated, including dodecanoic acid (VIP = 1.416, FC = 0.378, q = 0.043) and tridecane acid (VIP = 0.880, FC = 0.780, q = 0.106). Furthermore, increased levels of differential amino acids were found in LUAD samples. Conclusion: Lung cancer is a complex and heterogeneous disease with diverse genetic alterations. The study of metabolic profiles is a promising research field in this cancer type. Targeted and untargeted metabolomics revealed significant differences in metabolites between LUAD and NL tissues, including elevated levels of organic acids, decreased levels of fatty acids, and increased levels of amino acids. These metabolic features provide valuable insights into LUAD pathogenesis and can potentially serve as biomarkers for prognosis and therapy response.

Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma.

Background: Curcumin (CUR), an effective traditional Chinese medicinal extract, displays good anti-cancer activity against various cancers. Nevertheless, the impacts and fundamental mechanisms of CUR to treat esophageal squamous cell carcinoma (ESCC) yet to be comprehensively clarified. This study examined the suppressive impacts of CUR on ESCC. Methods: For a comprehensive understanding of the effect of CUR in ESCC. The CUR targets and ESCC-related genes were identified respectively, and the intersection targets between CUR and ESCC were acquired. Then, we examined the intersection targets and discovered genes that were expressed differently in ESCC. Using DAVID, enrichment analyses were conducted on the targets of CUR-ESCC. The STRING database and Cytoscape v.3.9.1 were utilized to build networks for protein-protein interaction (PPI) and drug-target-pathway. Furthermore, the interactions between CUR and its core targets were confirmed by molecular docking studies. To confirm the effects of CUR on ESCC cells, in vitro experiments were finally conducted. Results: Overall, 47 potential CUR targets for ESCC treatment were identified. The KEGG pathway enrichment analysis identified 61 signaling pathways, primarily associated with the FoxO signaling, the cell cycle, cellular senescence, the IL-17 signaling pathway which play important roles in ESCC progression. In the PPI network and the docking results identified CHEK1 and CDK6 as the core targets that positively associated with ESCC survival. CUR arrested ESCC cells at the G2/M and S phases, as shown by flow cytometry. Colony formation and CCK8 assays showed that CUR can inhibit the proliferative ability of ESCC cells. The Transwell invasion results validated that CUR can significantly inhibit the invasion rates of ESCC cells. Conclusion: Collectively, these findings indicate that CUR exhibits pharmacological effects on multiple targets and pathways in ESCC.