TRPV3-activated PARP1/AIFM1/MIF axis through oxidative stress contributes to atopic dermatitis.

TRPV3 is a temperature-sensitive calcium-permeable channel. In previous studies, we noticed prominent TUNEL-positive keratinocytes in patients with Olmsted syndrome and Trpv3+/G568V mice, both of which carry gain-of-function mutations in the TRPV3 gene. However, it remains unclear how the keratinocytes die and whether this process contributes to more skin disorders. Herein, we showed that gain-of-function mutation or pharmacological activation of TRPV3 resulted in PARP1/AIFM1/MIF axis-mediated parthanatos, which is an underestimated form of cell death in skin diseases. Chelating calcium, scavenging reactive oxygen species or inhibiting nitric oxide synthase effectively rescued the parthanatos, indicating that TRPV3 regulates parthanatos through calcium-mediated oxidative stress. Furthermore, inhibiting PARP1 downregulated TSLP and IL33 induced by TRPV3 activation in HaCaT cells, reduced immune cell infiltration, and ameliorated epidermal thickening in Trpv3+/G568V mice. Marked parthanatos was also detected in the skin of MC903-treated mice and patients with atopic dermatitis (AD), while inhibiting PARP1 largely alleviated the MC903-induced dermatitis. Additionally, stimulating parthanatos in mouse skin with methylnitronitrosoguanidine recapitulated many features of AD. These data demonstrate that the TRPV3-regulated parthanatos-associated PARP1/AIFM1/MIF axis is a critical contributor to the pathogenesis of Olmsted syndrome and AD, suggesting that modulating the PARP1/AIFM1/MIF axis is a promising therapy for these conditions.

Lever-enabled milli-Newton mechanical force detection via a microbottle resonator.

We demonstrate a milli-Newton mechanical force sensor based on a whispering gallery mode microbottle resonator (MBR). A lever model is established by coupling the MBR with a tapered fiber, whose ratio of load arm to effort arm (RLE) is flexibly adjusted to enlarge the detection range. The mechanical force is induced by attaching a capillary on the MBR stem and applying the downward displacement, which deforms the MBR's radius and thus shifts the resonance wavelength. The dependence of the capillary displacement on the mechanical force is theoretically deduced and verified. Experimentally, the sensors with different RLEs are built, and the maximum sensitivity of -10.48 pm/mN with a resolution of 40 µN is obtained. The achieved detection range is 0-4 mN, which depends on the capillary displacement and RLE of the lever. With the merits of easy fabrication and flexible structure, the proposed sensor shows great potential in biomedical and structural health monitoring.

Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

Effective dosage and mode of exercise for enhancing cognitive function in Alzheimer's disease and dementia: a systematic review and Bayesian Model-Based Network Meta-analysis of RCTs.

OBJECTIVE: Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. DESIGN: Systemic and Bayesian Model-Based Network Meta-Analysis. METHODS: In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD. RESULTS: Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362). CONCLUSION: Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer's disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.

IGF2BP1 Bolsters the Chondrocytes Ferroptosis of Osteoarthritis by Targeting m6A/MMP3 Axis.

Introduction: Chondrocyte degeneration and senescence are characteristics of osteoarthritis (OA) and other joint degenerative diseases, and ferroptosis has been observed to regulate the development of OA. However, the role of the N6-methyladenosine (m6A) modification in OA ferroptosis remains unclear. Methods: This study performed series of assays to investigate the function of the m6A reader IGF2BP1 in OA ferroptosis, including m6A quantitative analysis, Iron (Fe2+) release analysis, Malondialdehyde (MDA) measurement, lipid peroxidation (ROS) detection and Glutathione (GSH) measurement. The molecular interaction and mechanism analysis was performed by Luciferase reporter assay, mRNA stability analysis and RNA immunoprecipitation (RIP) assay. Results: These results indicate that IGF2BP1 is upregulated in IL-1ß-induced chondrocytes. Functionally, IGF2BP1 silencing represses ferroptosis, including iron (Fe2+) accumulation, malondialdehyde, and reactive oxygen species (ROS). Mechanistically, among the potential downstream targets, matrix metalloproteinase-3 (MMP3) was observed to harbor a significant m6A modified site in the 3'-UTR. IGF2BP1 combines with MMP3 through the binding of m6A sites, thereby enhancing MMP3 mRNA stability. Discussion: In conclusion, our findings revealed the functions and mechanisms of m6A regulator IGF2BP1 in OA chondrocyte's ferroptosis, providing a novel target for OA treatment.

Ewing sarcoma of the pancreas: a pediatric case report and narrative literature review.

Ewing's Sarcoma (ES) is an rare, small round-cell sarcoma that predominantly occurs in children and young adults, with both skeletal and extraskeletal manifestations. However, pancreatic ES, due to its rarity, is infrequently featured in scholarly literature, with only a scant 43 reported instances. Our study describes a case of pancreatic ES in an 8-year-old boy who was found to have an abdominal mass. Following an exhaustive examination, the boy was diagnosed with a neoplasm in the pancreatic head and underwent a complex surgical procedure encompassing pancreatoduodenectomy and partial transverse colectomy. Immunohistochemical assays confirmed the neoplastic cells' positivity for Cluster of Differentiation 99(CD99), Vimentin, and NK2 Homeobox 2(NKX2.2), while genomic testing identified an EWSR1-FLI1(Ewing Sarcoma Breakpoint Region 1-Friend Leukemia Integration 1) gene fusion. This led to a conclusive diagnosis of pancreatic Ewing's Sarcoma. The patient underwent seven cycles of adjuvant chemotherapy, alternating between VDC (Vincristine, Doxorubicin, Cyclophosphamide) and IE (Ifosfamide, Etoposide) tri-weekly, but did not undergo radiotherapy. At present, the patient remains neoplasm-free. Through our case analysis and comprehensive review of the existing literature, we aim to underscore th rarity of pancreatic Ewing's sarcoma and to highlight the efficacy of our individualized therapeutic approach.

Feasibility of Using Intraoperative Neurophysiological Monitoring for Detecting Bone Layer of Cervical Spine Surgery.

STUDY DESIGN: Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding. OBJECTIVE: To explore the feasibility of IONM to estimate bone layer thickness. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies. METHODS: Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared. RESULT: The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold. CONCLUSIONS: It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.

CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone.

BACKGROUND: Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs. METHODS: Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism. RESULTS: The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL-1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL-1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05). CONCLUSIONS: The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Reproducibility and reliability of pancreatic pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with an extended Tofts linear (ETL) model for tissue and tumor evaluation has been established, but its effectiveness in evaluating the pancreas remains uncertain. PURPOSE: To understand the pharmacokinetics of normal pancreas and serve as a reference for future studies of pancreatic diseases. MATERIAL AND METHODS: Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with the ETL model. First, intra- and inter-observer reliability was assessed through the use of the intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Second, a subgroup analysis of the pancreatic DCE-MRI pharmacokinetic parameters was carried out by dividing the 54 individuals into three groups based on the pancreatic region, three groups based on age, and two groups based on sex. RESULTS: There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, and vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. Only the pancreatic ve of the older group was higher than that of the young and middle-aged groups (P = 0.042, 0.001), and the vp of the pancreatic head was higher than that of the pancreatic body and tail (P = 0.014, 0.043). CONCLUSION: The application of DCE-MRI with an ETL model provides a reliable, robust, and reproducible means of non-invasively quantifying pancreatic pharmacokinetic parameters.

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview.

Drug-induced liver injury is a prevalent severe adverse event in clinical settings, leading to increased medical burdens for patients and presenting challenges for the development and commercialization of novel pharmaceuticals. Research has revealed a close association between gut microbiota and drug-induced liver injury in recent years. However, there has yet to be a consensus on the specific mechanism by which gut microbiota is involved in drug-induced liver injury. Gut microbiota may contribute to drug-induced liver injury by increasing intestinal permeability, disrupting intestinal metabolite homeostasis, and promoting inflammation and oxidative stress. Alterations in gut microbiota were found in drug-induced liver injury caused by antibiotics, psychotropic drugs, acetaminophen, antituberculosis drugs, and antithyroid drugs. Specific gut microbiota and their abundance are associated closely with the severity of drug-induced liver injury. Therefore, gut microbiota is expected to be a new target for the treatment of drug-induced liver injury. This review focuses on the association of gut microbiota with common hepatotoxic drugs and the potential mechanisms by which gut microbiota may contribute to the pathogenesis of drug-induced liver injury, providing a more comprehensive reference for the interaction between drug-induced liver injury and gut microbiota.

Arlenea delicata gen. et sp. nov., a new ephedroid plant from the Early Cretaceous Crato Formation, Araripe Basin, Northeast Brazil.

Ephedroid macrofossils have been widely documented in Cretaceous deposits, including numerous from the Lower Cretaceous Yixian Formation of NE China. However, few ephedroid macrofossils have been reported from South America. Herein, we describe a new plant of the family Ephedraceae, Arlenea delicata gen. et sp. nov., from the Lower Cretaceous Crato Formation of the Araripe Basin, Northeast Brazil, based on the vegetative and reproductive structures. It has the typical morphological characteristics of ephedroid plants, including fertile reproductive branches, opposite phyllotaxy, terminal female cones, a sympodial branching system, longitudinally striated internodes, and swollen nodes. Our new finding is unusual in having inner chlamydosperms subtended by two pairs of bracts, reproductive units connected to branches through swollen receptacles and a smooth seed surface. This new ephedroid taxon from the Crato Formation increases our understanding of plant diversity of this group during the Early Cretaceous. Furthermore, the general morphology (fleshy bracts and enlarged receptacles) of this new fossil discovery indicates that seeds of this plant may have been dispersed by animals such as pterosaurs (mainly the Tapejaridae) and birds (Enantiornithes and Ornituromorpha). If true, this would explain the cosmopolitan distribution of Ephedraceae in the Lower Cretaceous.

Non-O1, Non-O139 Vibrio cholerae Bacteremia in an Autoimmune Pancreatitis Patient.

Over 200 different serogroups of Vibrio cholerae based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139. Non-O1/non-O139 V. cholerae serogroups generally do not produce the cholera-causing toxin but do sporadically cause gastroenteritis and extra-intestinal infections. Recently, however, bloodstream infections caused by non-O1/non-O139 V. cholerae are being increasingly reported, and these infections are associated with high mortality in immunocompromised hosts. We describe a case of non-O1/non-O139 V. cholerae bacteremia in a patient with autoimmune pancreatitis and stenosis of the intra- and extrahepatic bile ducts. The clinical manifestations of bacteremia were fever and mild digestive symptoms. The blood cultures showed V. cholerae, which was identified as a non-O1, non-O139 serogroup by slide agglutination tests and PCR. The bloodstream infection of the patient was likely caused by the consumption of contaminated seafood at a banquet. The patient recovered after the administration of a third-generation cephalosporin. Non-O1/non-O139 V. cholerae infection presents with or without gastrointestinal manifestations; close attention should be paid to the possibility of disseminated non-O1/non-O139 V. cholerae infection in high-risk patients.

BnaPLDα1-BnaMPK6 Involved in NaCl-Mediated Overcoming of Self-Incompatibility in Brassica napus L.

Self-incompatibility (SI) is an important genetic mechanism exploited by numerous angiosperm species to prevent inbreeding. This mechanism has been widely used in the breeding of SI trilinear hybrids of Brassica napus. The SI responses in these hybrids can be overcome by using a salt (NaCl) solution, which is used for seed propagation in SI lines. However, the mechanism underlying the NaCl-induced breakdown of the SI response in B. napus remains unclear. Here, we investigated the role of two key proteins, BnaPLDα1 and BnaMPK6, in the breakdown of SI induced by NaCl. Pollen grain germination and seed set were reduced in BnaPLDα1 triple mutants following incompatible pollination with NaCl treatment. Conversely, SI responses were partially abolished by overexpression of BnaC05.PLDα1 without salt treatment. Furthermore, we observed that phosphatidic acid (PA) produced by BnaPLDα1 bound to B. napus BnaMPK6. The suppression and enhancement of the NaCl-induced breakdown of the SI response in B. napus were observed in BnaMPK6 quadruple mutants and BnaA05.MPK6 overexpression lines, respectively. Moreover, salt-induced stigmatic reactive oxygen species (ROS) accumulation had a minimal effect on the NaCl-induced breakdown of the SI response. In conclusion, our results demonstrate the essential role of the BnaPLDα1-PA-BnaMPK6 pathway in overcoming the SI response to salt treatment in SI B. napus. Additionally, our study provides new insights into the relationship between SI signaling and salt stress response. SIGNFICANCE STATEMENT: A new molecular mechanism underlying the breakdown of the NaCl-induced self-incompatibility (SI) response in B. napus has been discovered. It involves the induction of BnaPLDα1 expression by NaCl, followed by the activation of BnaMPK6 through the production of phosphatidic acid (PA) by BnaPLDα1. Ultimately, this pathway leads to the breakdown of SI. The involvement of the BnaPLDα1-PA-BnaMPK6 pathway in overcoming the SI response following NaCl treatment provides new insights into the relationship between SI signalling and the response to salt stress.

Prediction model to identify infectious COVID-19 patients in the emergency department.

Background: Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19. Objective: To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED. Material and methods: Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25). Results: Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data. Conclusion: Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.

Spectrum-effect relationship between HPLC fingerprints and antioxidant activity of Qi-Fu-Yin based on multiple statistical correlation analysis.

INTRODUCTION: Qi-Fu-Yin has been used to treat Alzheimer's disease (AD) in China. Oxidative stress has been recognized as a factor in AD progress. To date, there is no quality control method to ensure batch-to-batch consistency of Qi-Fu-Yin, and the potential antioxidant compounds in Qi-Fu-Yin remain uncertain. OBJECTIVES: The aim of this study is to identify the potential antioxidant compounds of Qi-Fu-Yin and establish quality control standards for Qi-Fu-Yin. METHODS: High-performance liquid chromatography was used to establish and quantify the fingerprints of Qi-Fu-Yin from various batches. Ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the common peaks. Bivariate correlation analysis, partial least squares regression analysis, and gray correlation analysis were used to establish the spectrum-effect relationship. RESULTS: Forty-nine common peaks were determined through the establishment of fingerprints. Among them, 35 common peaks were preliminarily characterized. The multiple statistical correlation analysis methods identified six compounds as potential antioxidant constituents of Qi-Fu-Yin, and their antioxidant activities were validated in vitro. All six antioxidant compounds derived from two herbs. Therefore, three chemical index compounds derived from other three herbs were added to the quantitative analysis, while for two herbs, no peaks could be included. Eventually, six antioxidant constituents and three index compounds were quantitatively determined to provide a relatively comprehensive quality control for Qi-Fu-Yin. CONCLUSIONS: The study elucidated the antioxidant substance basis of Qi-Fu-Yin and provided a relatively comprehensive approach for the assay of Qi-Fu-Yin, which is a promising advance in the quality control of Qi-Fu-Yin.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Piezoelectrically-activated antibacterial catheter for prevention of urinary tract infections in an on-demand manner.

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.