Organophosphate flame retardants (OPFRs) have been widely used as the main alternatives to bromine-based flame retardants, resulting in their widespread detection in environmental media and even in human blood. The potential health risks arising therefrom, particularly the direct impacts on the blood system, have become a focus in the field of environmental health. This article systematically reviewed the latest research progress on the hematotoxicity of OPFRs, covering three core aspects: the toxic effects aspect, which systematically elaborated on the bidirectional interference of OPFRs with coagulation function, their toxic effects on the hematopoietic system, and their disruptive effects on blood biochemical metabolism; the mechanistic analysis aspect, which dissected the multi-pathway, multi-target toxic mechanism network of OPFRs, including common pathways based on oxidative stress and inflammatory responses, the direct and indirect regulation of coagulation function mediated by nuclear receptors and endocrine disruption, and the disturbance of blood cell production at the source through disruption of the hematopoietic microenvironment; and the risk assessment aspect, which, in response to the limitations of traditional methods, focused on the application prospects and core advantages of novel approaches based on structure-activity relationships in filling data gaps and achieving precise risk prediction. This review aims to systematically summarize the research progress on the mechanisms of OPFR-induced hematotoxicity, providing systematic theoretical support for subsequent in-depth mechanistic studies, targeted epidemiological investigations, and the optimization of risk assessment models.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Objective:To investigate the feasibility of transcatheter edge-to-edge repair (TEER) using a short-clip strategy for patients with moderate-to-severe or greater degenerative mitral regurgitation caused by commissural prolapse.Methods:This retrospective study included patients with severe mitral regurgitation secondary to commissural prolapse who underwent TEER at the Second Affiliated Hospital of Zhejiang University School of Medicine between September 2022 and July 2024. Preoperative clinical and imaging data, intraoperative details, procedural outcomes, and 1-month postoperative follow-up results were collected.Results:A total of 19 patients were enrolled, aged (74.1±6.1) years, including 12 males. Among them, 10 patients had external commissural prolapse, and 9 patients had internal commissural prolapse. Preoperatively, all patients exhibited severe mitral regurgitation (4+), with an effective regurgitant orifice area of (0.55±0.17) cm2, left atrial volume of (104.77±36.57) ml, left ventricular end-diastolic volume of (102.29±32.47) ml, left ventricular end-diastolic dimension of (5.34±0.59) mm, and prolapse width of (1.18±0.34) cm. All procedures utilized short clips (NTR or NTW clips) to target the prolapsed commissural region and were completed successfully without intraoperative complications. At 1-month follow-up, no mortality, stroke, single-leaflet device attachment, myocardial infarction, or unplanned mitral reintervention occurred. Mitral regurgitation severity improved to ≤2+ in all patients, with left atrial volume of (74.49±33.83) ml, left ventricular end-diastolic volume of (85.90±18.05) ml, and left ventricular end-diastolic dimension of (4.93±0.37) mm (all P<0.05). Conclusion:The short-clip strategy, focusing on precise clip placement at the commissural interface, is feasible and effective for TEER in patients with severe mitral regurgitation due to commissural prolapse.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Based on WANG Xugao's"thirty liver-regulating methods,"this paper summarized the clinical thinking of treating diabetic kidney disease from the liver.The liver is closely associated with the pathogenesis of diabetic kidney disease,including internal heat,essence depletion,latent wind,and the accumulation and dissipation of a conglomeration of kidney collateral zhengjia.WANG Xugao's"thirty liver-regulating methods"comprehensively reveals the physiological and pathological changes of the liver,as well as clinical approaches for liver treatment.Liver qi stagnation can lead to the generation of internal heat,liver stagnation and deficiency can cause essence depletion and collateral obstruction,and disharmony of the liver wood can cause internal wind disturbance,which all contribute to the progression of diabetic kidney disease at different stages.Treatment generally follows the essence of"thirty liver-regulating methods."In the early stage,treatment should focus on treating liver heat by soothing the liver qi,clearing the liver fire,and removing damp-heat to resolve stagnation and heat.In the middle stage,treatment should focus on treating liver deficiency by nourishing the liver yin to clear heat,replenishing the essence and blood to tonify deficiency,and promoting blood circulation to remove stasis,thereby strengthening the foundation and nurturing the primal essence.In the later stage,treatment should focus on treating liver wind to prevent complications and improve the patient's quality of life.Throughout the entire process,liver collaterals are treated using pungent herbs to invigorate qi and open the liver channels,relieving blood stasis and promoting circulation.In conjunction with the above methods,flexible selection of effective formulas and drug pairs should be used,each addressing specific treatment goals.

Diabetic kidney disease(DKD),a prevalent complication of diabetes mellitus,remains a leading cause of end-stage renal disease.Recent research has identified lipophagy,a novel mechanism in DKD pathogenesis,drawing increasing attention in the field.This paper explores the biological connotation of the"internal heat leading to Zheng"pathogenesis based on lipophagy.The study proposes that lipophagy represents the microscopic biological correlation of liver-spleen coordination in regulating spleen transport and the ascending-descending dynamics of the middle jiao.Under persistent hyperglycemia,the suppression of lipophagic activity mirrors the traditional Chinese medicine(TCM)pathophysiological process described as"excessive fire consuming healthy qi,"whereas aberrant lipid accumulation in the kidney corresponds to the dynamic aggregation and dispersion of micro-zhengjia.Lipotoxicity,a key driver of DKD progression,is interpreted as the biological manifestation of accumulated turbidity transforming into toxicity,resulting in progressive impairment of renal essence and function.The dynamic process of lipophagy dysfunction under hyperglycemia,marked by renal microangiopathy,glomerular and tubular dysfunction,and renal fibrosis,closely mirrors the pathological evolution of"micro-zhengjia"and"internal heat leading to Zheng."Consequently,TCM strategies for DKD prevention and treatment should emphasize heat regulation,stage-specific interventions,liver-spleen harmonization,metabolic modulation,early collateral protection,and blood-activating approaches.

Objective To investigate the association between cerebrospinal fluid(CSF)oligoclonal band(OCB)positivity and clinical manifestations in patients with neuromyelitis optica spectrum disorder(NMOSD).Methods A retrospective analysis of clinical data from patients with NMOSD treated at our hospital from May 2019 to January 2024 was conducted.Based on OCB test results,patients were categorized into OCB-positive and OCB-negative groups.We compared baseline characteristics between the two groups and analyzed the relationship between clinical features and OCB positivity.Results This study included a total of 62 patients,comprising 17 in the OCB+group and 45 in the OCB-group.Compared with the OCB-group,patients in the OCB+group exhibited more pronounced central nervous system inflammatory features.Specifically,OCB+group had significantly higher proportions of patients with cerebrospinal fluid white blood cell counts>8×10?/L(64.7%vs.26.7%,P=0.003)and elevated immunoglobulin indices(0.72 vs.0.61,P=0.037).Additionally,the OCB+group exhibited more complex and diverse clinical presentations.Specifically,this group showed a higher incidence of mild consciousness impairment during the acute phase(P=0.005)and a greater tendency to present with multiple core symptoms(≥3 core symptoms)occurring concurrently(52.9%vs.20.0%,P=0.025)and misdiagnosis(29.4%vs.8.9%,P=0.101).This was particularly notable when comparing to acute myelitis involving the cervical spinal cord(82.4%vs.53.3%,P=0.036)and acute diencephalic syndrome[41.2%vs.6.7%,P=0.004,including hyponatremia(35.3%vs.8.9%,P=0.033)].Multivariate logistic regression analysis demonstrated that OCB positivity(OR=3.895,95%CI:1.065-14.249)was significantly associated with the presence of multiple core symptoms.Conclusion In acute-phase NMOSD patients,OCB+is associated with significantly higher rates of co-occurrence of multiple core symptoms(≥3 core symptoms)and misdiagnosis.Notably,acute myelitis involving the cervical spinal cord and acute diencephalic clinical syndrome are particularly prevalent in this OCB+subgroup.The clinical manifestations are complex and diverse,suggesting the need for enhanced clinical identification and timely intervention.