KRAS Gene Mutation Associated with Grade of Tumor Budding and Peripheral Immunoinflammatory Indices in Patients with Colorectal Cancer.

Background: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC. Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed. Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287-3.016, p=0.002), and high SII level (≥807.81 vs <807.81, OR: 1.915, 95% CI: 1.120-3.272, p=0.018) were independently associated with KRAS mutation. Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.

Evaluation and analysis of risk factors for adverse events of the fractured vertebra post-percutaneous kyphoplasty: a retrospective cohort study using multiple machine learning models.

BACKGROUND: Adverse events of the fractured vertebra (AEFV) post-percutaneous kyphoplasty (PKP) can lead to recurrent pain and neurological damage, which considerably affect the prognosis of patients and the quality of life. This study aimed to analyze the risk factors of AEFV and develop and select the optimal risk prediction model for AEFV to provide guidance for the prevention of this condition and enhancement of clinical outcomes. METHODS: This work included 383 patients with primary osteoporotic vertebral compression fracture (OVCF) who underwent PKP. The patients were grouped based on the occurrence of AEFV postsurgery, and data were collected. Group comparisons and correlation analysis were conducted to identify potential risk factors, which were then included in the five prediction models. The performance indicators served as basis for the selection of the best model. RESULTS: Multivariate logistic regression analysis revealed the following independent risk factors for AEFV: kissing spine (odds ratio (OR) = 8.47, 95% confidence interval (CI) 1.46-49.02), high paravertebral muscle fat infiltration grade (OR = 29.19, 95% CI 4.83-176.04), vertebral body computed tomography value (OR = 0.02, 95% CI 0.003-0.13, P < 0.001), and large Cobb change (OR = 5.31, 95% CI 1.77-15.77). The support vector machine (SVM) model exhibited the best performance in the prediction of the risk of AEFV. CONCLUSION: Four independent risk factors were identified of AEFV, and five risk prediction models that can aid clinicians in the accurate identification of high-risk patients and prediction of the occurrence of AEFV were developed.

Proteomics of severe SARS-COV-2 infection and paraquat poisoning in human lung tissue samples: comparison of microbial infected and toxic pulmonary fibrosis.

Introduction: Pulmonary fibrosis (PF) encompasses a spectrum of lung conditions characterized by the abnormal accumulation of scar tissue in the lungs, leading to impaired respiratory function. Various conditions can result in severe PF, among which viral infections have emerged as significant triggers. In addition to viral infections, exposure to toxic substances such as paraquat represents another significant risk factor for PF. Therefore, this study aimed to explore the dissimilarities and similarities between PF triggered by viral infections and chemical toxicants, using the mechanism of PF in IPF as a reference. Methods: Data-independent acquisition proteomics technology was employed to identify COVID-19 and paraquat-induced PF from the autopsy of lung tissue samples obtained from individuals who died due to PF. Bioinformatics was employed for differential protein analysis, and selected indicators were validated on pathological sections. Results: Our results showed that the differential proteins associated with the two causes of PF were enriched in similar lung fibrosis-related signaling pathways, such as the Wnt signaling pathway. However, differences were observed in proteins such as CACYBP, we verified the consistency of the results with proteomics using the IHC approach. Conclusion: This study illuminates distinct protein-level differences by investigating pulmonary fibrosis pathways in severe COVID-19 and paraquat poisoning. Although both conditions activate lung-protective and repair pathways, COVID-19 shows limited phosphorylation-independent ubiquitination of ß-catenin compared to paraquat toxicity. These findings shed light on potential therapeutic targets for PF induced via diverse factors.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Comparison of Clinical Manifestations and Related Factors of Hepatocellular Carcinoma with Chronic Hepatitis B.

Background: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC. Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV. Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥500 copies/mL were significantly higher in the HCC group than in the controls (all p<0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥60 years (OR: 1.835, 95% CI: 1.020-3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796-17.288, p<0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106-4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001-1.007, p=0.002) were risk factors for HCC in patients with CHB. Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Results: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). Conclusion: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Establishment of Facial Nerve Injury Rat Model for Idiopathic Facial Paralysis Research.

Idiopathic facial paralysis is the most common type of facial nerve injury, accounting for approximately 70% of peripheral facial paralysis cases. This disease can not only lead to a change in facial expression but also greatly impact the psychology of patients. In severe cases, it can affect the normal work and life of patients. Therefore, the research on facial nerve injury repair has important clinical significance. In order to study the mechanism of this disease, it is necessary to carry out relevant animal experiments, among which the most important task is to establish an animal model with the same pathogenesis as human disease. The compression of the facial nerve within the petrous bone, especially the nerve trunk at the junction of the distal end of the internal auditory canal and the labyrinthine segment, is the pathogenesis of idiopathic facial paralysis. In order to simulate this common disease, a compression injury model of the main extracranial segment of the facial nerve was established in this study. The neurological damage was evaluated by behavioral, neuroelectrophysiological, and histological examination. Finally, 50 g constant force and 90 s clamp injury were selected as the injury parameters to construct a stable idiopathic facial paralysis model.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin.

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

Aldehyde dehydrogenase 2 rs671 a/A Genotype is Associated with an Increased Risk of Early Onset Coronary Artery Stenosis.

Background: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤55 years old in men and ≤65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study. Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk. Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130-5.569, p=0.024), overweight (BMI≥24.0 vs 18.5-23.9: OR 5.047, 95% CI: 3.275-7.777, p<0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595-4.961, p<0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397-3.437, p=0.001) were the independent risk factors of early onset CAS. Conclusion: In men ≤55 years old and women ≤65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.

Facilely Prepared Carbon Dots as Effective Anode Modifier for Enhanced Performance of Microbial Fuel Cells.

Microbial fuel cells (MFCs) are a promising technology for obtaining energy in wastewater. Effective extracellular electron transfer is one of the key factors for its practical application. In this work, carbon dots (CDs) enriched with oxygen-containing groups on the surface were synthesized as an efficient anode modifier using a simple hydrothermal method and common reactants. The experimental findings indicated that anodes modified with CDs exhibited increased electrical conductivity and greater hydrophilicity. These modifications facilitated increased microorganism loading and contributed to enhancing electrochemical processes within the anode biofilm. The CD-modified MFCs exhibited higher maximum power density (661.1 ± 42.6 mW·m-2) and open-circuit voltage (534.50 ± 6.4 mV), which were significantly better than those of the blank group MFCs (484.1 ± 14.1 mW·m-2 and 447.50 ± 12.1 mV). The use of simple carbon materials to improve the microbial loading on the MFCs anode and the electron transfer between the microbial-electrode may provide a new idea for the design of efficient MFCs.

Recent Advancement in Inhaled Nano-drug Delivery for Pulmonary, Nasal, and Nose-to-brain Diseases.

Pulmonary, nasal, and nose-to-brain diseases involve clinical approaches, such as bronchodilators, inhaled steroids, oxygen therapy, antibiotics, antihistamines, nasal steroids, decongestants, intranasal drug delivery, neurostimulation, and surgery to treat patients. However, systemic medicines have serious adverse effects, necessitating the development of inhaled formulations that allow precise drug delivery to the airways with minimum systemic drug exposure. Particle size, surface charge, biocompatibility, drug capacity, and mucoadhesive are unique chemical and physical features that must be considered for pulmonary and nasal delivery routes due to anatomical and permeability considerations. The traditional management of numerous chronic diseases has a variety of drawbacks. As a result, targeted medicine delivery systems that employ nanotechnology enhancer drug efficiency and optimize the overall outcome are created. The pulmonary route is one of the most essential targeted drug delivery systems because it allows the administering of drugs locally and systemically to the lungs, nasal cavity, and brain. Furthermore, the lungs' beneficial characteristics, such as their ability to inhibit first-pass metabolism and their thin epithelial layer, help treat several health complications. The potential to serve as noninvasive self-administration delivery sites of the lung and nasal routes is discussed in this script. New methods for treating respiratory and some systemic diseases with inhalation have been explored and highlight particular attention to using specialized nanocarriers for delivering various drugs via the nasal and pulmonary pathways. The design and development of inhaled nanomedicine for pulmonary, nasal, and respiratory medicine applications is a potential approach for clinical translation.

Effects of ondansetron treatment on outcomes of critically ill patients with myocardial infarction partly through its anti-inflammatory activity.

Background: Patients with myocardial infarction (MI) in intensive care units (ICU) are at high risk of death. Whether treatment with ondansetron (OND) at an early stage plays a protective role in critically ill patients with MI and its underlying mechanism remains unclear. Methods: A total of 4486 patients with MI were enrolled in the study cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into OND-medication groups or not. Propensity score matching (PSM) and regression analysis were performed to investigate the effect of OND on patients, accompanied by sensitivity analysis to evaluate the robustness of the results. Integrated with causal mediation analysis (CMA), we investigated the potential causal pathway mediated by the palate-to-lymphocyte ratio (PLR) between early OND treatment and clinical outcomes. Results: Among patients with MI, 976 of them were treated with OND at the early stage while 3510 patients were not. The all-cause in-hospital mortality rate was significantly lower in the OND-medication group (5.6% vs 7.7%), accompanied by lower 28-day mortality (7.8% vs 11.3%) and 90-day mortality (9.2% vs 13.1%) rates. PSM analysis further confirmed the results for in-hospital mortality (5.7% vs 8.0%), 28-day mortality (7.8% vs 10.8%), and 90-day mortality (9.2% vs 12.5%). After adjusting for confounders, multivariate logistic regression analysis revealed that OND was associated with decreased in-hospital mortality (OR = 0.67, 95% CI: 0.49-0.91), and Cox regression confirmed the results for 28-day mortality and 90-day mortality with HR = 0.71 and 0.73, respectively. Most importantly, CMA demonstrated that the protective effect of OND on patients with MI was mediated by its anti-inflammatory effect through the regulation of PLR. Conclusion: Early use of OND in critically ill patients with MI may exert protective effects by reducing in-hospital mortality and 28- and 90-day mortality. The beneficial effects of OND on these patients were exerted through anti-inflammatory effects, at least in part.

[Simultaneous determination of 22 antibiotics in environmental water samples by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry].

The widespread and frequent use of antibiotics to treat diseases or encourage animal growth has resulted in their persistence and accumulation in water, soil, and sediments. As a typical emerging pollutant in the environment, antibiotics have become an important research focus in recent years. Antibiotics are commonly found at trace levels in water environments. Unfortunately, the determination of various types of antibiotics, all of which exhibit different physicochemical properties, remains a challenging endeavor. Thus, developing pretreatment and analytical techniques to achieve the rapid, sensitive, and accurate analysis of these emerging contaminants in various water samples is an essential undertaking.In this paper, a solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for the simultaneous determination of 22 antibiotics including 4 penicillins, 12 quinolones and 6 macrolides in environmental water samples was developed. Based on the characteristics of the screened antibiotics and sample matrix, the pretreatment method was optimized, focusing on the SPE column, pH of the water sample, and amount of ethylene diamine tetra-acetic acid disodium (Na2EDTA) added to the water sample. Prior to extraction, a 200 mL water sample was added with 0.5 g of Na2EDTA and pH-adjusted to 3 using sulfuric acid or sodium hydroxide solution. Water sample enrichment and purification were achieved using an HLB column. HPLC separation was carried out on a C18 column (100 mm×2.1 mm, 3.5 µm) via gradient elution with a mobile phase composed of acetonitrile and 0.15% (v/v) formic acid aqueous solution. Qualitative and quantitative analyses were performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source. The results showed correlation coefficients greater than 0.995, indicating good linear relationships. The method detection limits (MDLs) and limits of quantification (LOQs) were in the ranges of 2.3-10.7 ng/L and 9.2-42.8 ng/L, respectively. The recoveries of target compounds in surface water at three spiked levels ranged from 61.2% to 157%, with relative standard deviations (RSDs) of 1.0%-21.9%. The recoveries of target compounds in wastewater at three spiked levels were 50.1%-129%, with RSDs of 1.2%-16.9%. The method was successfully applied to the simultaneous determination of antibiotics in reservoir water, surface water, sewage treatment plant outfall, and livestock wastewater. Most of the antibiotics were detected in watershed and livestock wastewater. Lincomycin was detected in 10 surface water samples, with a detection frequency of 90%, and ofloxacin showed the highest contents (127 ng/L) in livestock wastewater. Therefore, the present method exhibits excellent performance in terms of MDLs and recoveries compared with previously reported methods. The developed method presents the advantages of small water sample volumes, wide applicability, and fast analysis times; thus, it can be considered a rapid, efficient, and sensitive analytical method with excellent potential for monitoring emergency environmental pollution. The method could also provide a reliable reference for formulating antibiotic residue standards. The results provide strong support for and an improved understanding of the environmental occurrence, treatment, and control of emerging pollutants.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

The preliminary development and psychometric properties of the Psychotherapy Side Effects Scale.

BACKGROUND: Side effects in psychotherapy are common and have a negative impact on patients or clients. However, effective evaluation tools are still lacking and have not been fully studied. The present study aims to develop a scale with good reliability and validity to measure the side effects of psychotherapy. METHODS: The 25 items in the Psychotherapy Side Effects Scale (PSES) were condensed and distributed to 420 subjects online to test its psychometric properties. RESULTS: The internal consistency of the PSES was satisfactory to excellent (Cronbach's ɑ coefficient was .95, and the Guttman split-half coefficient was 0.88). A statistically significant negative correlation between the satisfaction score and the total score of the PSES was shown (r = -0.51, p < .001). The PSES could effectively discriminate between two groups with and without side effects (F = 250.95, p < .001) and was able to predict the occurrence of side effects in psychotherapy with an area under curve of 0.932 and a 95% confidence interval of 0.900-0.964 (p < .001). A cutoff was set at 36 points in total PSES score, from which the maximum Youden's index (= 0.72) could be obtained. The positive rate of the PSES was 24% (101/420). CONCLUSION: The PSES showed good internal consistency, content validity, concurrent validity, discriminant validity and predictive validity in evaluating and identifying side effects in psychotherapy. More advanced reliability testing methods and structural validity testing for PESE need to be practiced in the future to better serve clinical practice.

An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

More than just statics: altered complexity of dynamic amplitude of low-frequency fluctuations in the resting brain after stroke.

Objective.Previous neuroimaging studies mainly focused on static characteristics of brain activity, and little is known about its characteristics over time, especially in post-stroke (PS) patients. In this study, we aimed to investigate the static and dynamic characteristics of brain activity after stroke using functional magnetic resonance imaging (fMRI).Approach.Twenty ischemic PS patients and nineteen healthy controls (HCs) were recruited to receive a resting-state fMRI scanning. The static amplitude of low-frequency fluctuations (sALFFs) and fuzzy entropy of dynamic ALFF (FE-dALFF) were applied to identify the stroke-induced alterations.Main results.Compared with the HCs, PS patients showed significantly increased FE-dALFF values in the right angular gyrus (ANG), bilateral precuneus (PCUN), and right inferior parietal lobule (IPL) as well as significantly decreased FE-dALFF values in the right postcentral gyrus (PoCG), right dorsolateral superior frontal gyrus (SFGdor), and right precentral gyrus (PreCG). The receiver operating characteristic analyses demonstrated that FE-dALFF and sALFF possess comparable sensitivity in distinguishing PS patients from the HCs. Moreover, a significantly positive correlation was observed between the FE-dALFF values and the Fugl-Meyer Assessment (FMA) scores in the right SFGdor (r= 0.547), right IPL (r= 0.522), and right PCUN (r= 0.486).Significance.This study provided insight into the stroke-induced alterations in static and dynamic characteristics of local brain activity, highlighting the potential of FE-dALFF in understanding neurophysiological mechanisms and evaluating pathological changes.

T2 mapping and readout segmentation of long variable echo-train diffusion-weighted imaging for the differentiation of parotid gland tumors.

OBJECTIVE: To investigate the diagnostic value of radial turbo-spin-echo (TSE) T2 mapping and readout segmentation of long variable echo-train diffusion-weighted imaging (RESOLVE DWI) for the differentiation of parotid gland tumors. MATERIALS AND METHODS: One hundred and fifty-four patients with histopathologically confirmed parotid gland tumors were retrospectively recruited from June 2018 to May 2021 at the First Affiliated Hospital of Zhengzhou University. There were 111 benign tumors and 43 malignant tumors. Benign tumors were further divided into pleomorphic adenomas (n = 69) and Warthin's tumors (n = 26). All patients were scanned using T2 mapping and RESOLVE DWI. T2 and ADC values and a combination of the two methods were compared and analyzed for the ability to differentiate parotid gland tumor types. RESULTS: The T2 and ADC values of benign tumors were significantly higher than those of the malignant tumors (127.97 ± 56.29 ms vs 97.53 ± 45.24 ms, 1.27 ± 0.40 × 10-3 mm2/s vs 1.00 ± 0.39 × 10-3 mm2/s, all P < 0.05). The area under the curve (AUC) of the T2 and ADC values for differentiating (1) benign and malignant parotid tumors, (2) pleomorphic adenomas and Warthin's tumors, (3) pleomorphic adenomas and malignant tumors, and (4) Warthin's tumors and malignant tumors were 0.709 and 0.715, 0.918 and 0.994, 0.748 and 0.774, and 0.665 and 0.659, respectively, with no significant differences observed between the T2 and ADC values (all P > 0.05). There were no significant differences in these values among the three tumor groups (malignant tumor, pleomorphic adenoma, and Warthin's tumor groups, all P > 0.05). CONCLUSIONS: T2 mapping and RESOLVE DWI can be used to differentiate various parotid gland tumors. T2 values are comparable to ADC values.

Circular RNA detection methods: A minireview.

Circular RNA (circRNA), a novel type of covalently closed RNA, is implicated in several developmental and metabolic disease processes. CircRNAs exhibit tissue-specific expression, and are stable, abundant, and highly conserved, making them ideal biomarkers for diagnosis and prognosis. Accurate profiling of circRNA, however, is a prerequisite for their clinical application. Traditional methods such as northern blotting, RT-qPCR, and microarray analysis provide useful but limited information. To address these issues, a number of novel assays have recently emerged, such as droplet digital PCR (ddPCR), isothermal exponential amplification, and rolling cycle amplification, which increase the sensitivity and specificity of circRNA detection. Herein, we summarize the advantages and limitations of the new detection methods and discuss the challenges as well as future directions.