This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

BACKGROUND: Prior studies have shown that drivers with type 2 diabetes are more likely to be involved in motor vehicle collisions (MVCs) compared to the general population. Certain meteorological factors have been increasingly recognized as contributors to MVC risk. This study aims to examine the association of MVCs with temperature, rainfall, wind speed, and sunshine duration among drivers with type 2 diabetes. METHODS: Using Taiwan's National Health Insurance data (2019-2021), we identified individuals diagnosed with type 2 diabetes and linked their records to the Police-Reported Traffic Accident Registry to obtain daily MVC counts. Meteorological data were sourced from the Central Weather Administration. Associations between daily weather conditions and MVCs were assessed using a Distributed Lag Non-Linear Model. RESULTS: Over the 1,096-day study period, 170,468 MVC events involving drivers with type 2 diabetes were recorded. A U-shaped association was observed between same-day temperature and MVC rates. Compared with the reference temperature of 17.5 °C, both lower temperatures (≤15 °C; rate ratio [RR] = 1.014-1.053) and higher temperatures (≥30 °C; RR = 1.062) were associated with increased MVC risk. Rainfall showed an inverse relationship with MVCs. Compared with 70 mm of rainfall, the lowest MVC rate occurred at 129 mm (RR = 0.873), while the highest was on rain-free days (0 mm; RR = 1.068). Stronger effects were observed when lag periods up to 14 days were considered. Wind speed and sunshine duration were not significantly associated with MVC risk. CONCLUSIONS These findings suggest that drivers with type 2 diabetes should exercise greater caution on days with extreme temperatures or in days with lesser rainfall, as these conditions may elevate MVC risk.
Humans ; Diabetes Mellitus, Type 2/epidemiology* ; Taiwan/epidemiology* ; Accidents, Traffic/statistics & numerical data* ; Male ; Middle Aged ; Female ; Weather ; Aged ; Adult ; Temperature ; Risk Factors

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective To explore the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP),and reveal its mechanism of resistance to ceftazidime/avibactam(CZA).Methods CZA-re-sistant CRKP strains initially isolated from the Affiliated Hospital of Xuzhou Medical University from January 2021 to September 2023 were collected.The carriage of 5 carbapenemase genes(blaKPC,blaNDM,blaOXA,blaVIM,blaIMp)were detected with gene amplification method and colloidal gold method.The relative copy number and expression level of Klebsiella pneumoniae(KP)carbapenemase-producing KP(KPC-KP)was detected with real-time quantita-tive polymerase chain reaction(RT-qPCR),mutation sites of KPC mutation strains were analyzed with whole-ge-nome sequencing,and epidemic characteristics of CRKP and resistance mechanism to CZA were analyzed.Results A total of 73 CZA-resistant CRKP strains were isolated,with 37(50.68％)being KPC and NDM co-producing strains,33(45.21％)NDM-producing alone(23 strains producing NDM-5 and 10 strains producing NDM-1),and 3 KPC-producing alone.KP-2842 strain was identified as ST11-type KPC-33 variant,KP-2127 and KP-2189 strains produced KPC-2.Compared with KP ATCC BAA-1705,the copy number of blaKPC in these strains up-regulated by 1.04-3.86 fold,and the expression increased by 6.66-12.93 fold,respectively.Colloidal gold and PCR methods demonstrated good consistency and the ability to detect the enzyme co-producing and KPC-33 variant.Conclusion In this hospital,the resistance of CRKP to CZA is primarily mediated by the metalloenzyme NDM,with co-produc-tion of NDM and KPC being a characteristic of CRKP.High copy number and expression level of blaKPC-2 also con-tribute to CZA resistance.This study identified the KPC-33 variant for the first time in ST11-type CRKP in Jiangsu Province.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

This article summarizes the domestic and international research progress of recombinant human follicle stimulating hormone(rFSH).According to relevant guidelines and application cases,the general requirements and common problems for non-clinical evaluation of rFSH are summarized.The clinical development prospects of long-acting rFSH products which is a hot research topic in recent years are analyzed and corresponding suggestions are given in order to provide reference for related work.

Objective:To explore the effects of Zhiyan mixture on the activation of classically activated macrophages(M1)and T helper cells 2(Th2)immune responses in mice with mycoplasma pneumoniae(MP)infection.Methods:C57BL/6J mice were divided into control group,MP group,Zhiyan mixture group and azithromycin group.Except control group,models of MP infection were prepared by nasal drip of MP bacterial solution(1×107 CFUs/ml)in the other groups.Zhiyan mixture group was given intragastric administration of Zhiyan mixture,azithromycin group was given intragastric administration of azithromycin,control group and MP group were given the same volume of normal saline.The pathological damage of lung tissues were observed by HE staining,and patho-logical scoring was conducted.The changes of MP load in lung tissues were detected by solid culture method.M1 level was detected by flow cytometry.The mRNA levels of inducible nitric oxide synthase(iNOS),TNF-α and CXC chemokine 1(CXCL1)in lung tissues were detected by PCR.The levels of IL-4,IL-5,IL-10 and IL-13 in lung tissues were detected by ELISA.The expressions of NF-κB pathway-related proteins in lung tissues were detected by Western blot.Results:The pathological scores of lung tissues,MP load,F4/80+cell level,ratios of CD86+/F4/80+and MHC Ⅱ+/F4/80+,and mRNA levels of iNOS,TNF-α and CXCL1 in MP group,Zhiyan mix-ture group and azithromycin group were higher than those in control group(P<0.05),levels of IL-4,IL-5,IL-10 and IL-13,and ex-pressions of p-p65/p65 and p-IKK/IKK in lung tissues were all higher than those in control group(P<0.05).The pathological scores of lung tissues,MP load,F4/80+level,ratios of CD86+/F4/80+and MHC Ⅱ+/F4/80+,and mRNA levels of iNOS,TNF-α and CXCL1 in Zhiyan mixture group and azithromycin group were lower than those in MP group(P<0.05),levels of IL-4,IL-5,IL-10 and IL-13 were higher than those in MP group(P<0.05),and protein expressions of p-p65/p65 and p-IKK/IKK in lung tissues were lower than those in MP group(P<0.05).Conclusion:Zhiyan mixture can improve lung injury in mice with MP infection,which may be related to reducing M1 activity,increasing Th2 immune response and inhibiting NF-κB pathway.