Molar-incisor hypomineralization (MIH) is a developmental defect of enamel that is characterized primarily by abnormal enamel mineralization affecting the first permanent molars and permanent incisors. Due to insufficient mineralization, teeth affected by MIH are prone to post-eruptive breakdown and caries, potentially leading to sequelae such as tooth sensitivity and occlusal problems. The diagnosis of MIH is primarily based on relevant perinatal and infantile medical history, the characteristic distribution of affected teeth, and the morphological features of the enamel defects. Based on the extent and severity of the enamel defect, MIH is classified as mild or severe. Diagnosis and treatment strategies emphasize early screening, diagnosis, and intervention, prioritizing prevention, providing symptomatic care, and implementing regular recall assessments. Mild MIH predominantly manifests as demineralized enamel opacities or discoloration, typically without significant enamel breakdown. Treatment focuses on caries prevention and aesthetic restoration, employing techniques such as remineralization, micro-abrasion, resin infiltration, bleaching, fluoride application, and fissure sealants. Severe MIH typically presents with extensive enamel opacities accompanied by substantial enamel breakdown and may be complicated by caries and tooth sensitivity. Management primarily involves restoring the structural defects or, for teeth that cannot be preserved, extraction followed by orthodontic treatment. Comprehensive management often requires a multimodal approach integrating various therapeutic modalities to restore both the function and aesthetics of the affected teeth and overall dentition. This article provides a review of advancements in diagnosis and the treatment strategies for MIH, offering a reference for clinical practice.

ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P＜0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P＜0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P＜0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P＜0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P＜0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P＜0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P＜0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P＜0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.

Objective:To investigate the correlation between statins and contrast-induced acute kidney injury (CI-AKI) and provide a reference basis for clinical practice.Methods:It was a retrospective cohort study. The adult patients were admitted to Peking University First Hospital from January 1, 2018, to December 31, 2020, and received at least one intravascular iodinated contrast administration during hospitalization. The clinical data of the patients were collected. The enrolled patients were divided into statin group and non-statin group according to statin exposure. The exposure of statins was defined as use of any type of statins within 48 hours before iodinated contrast administration. The primary outcome was in-hospital AKI defined as AKI developed after contrast administration and before discharge, with 30 days as the endpoint observation time, and the secondary outcome was post-contrast AKI (PC-AKI) defined as AKI onset within 72 hours after contrast administration. Cox regression model was applied to investigate the correlation between statin prescription prior to contrast administration and clinical outcomes. Pre-specified interaction analysis was conducted to examine modification effect of age, gender, baseline estimated glomerular filtration rate (eGFR), diabetes and the injection method of contrast.Results:Among 10 321 enrolled patients, the age was 63 (54, 71) years old, and 6 274 (60.8%) patients were males. There were 2 372 (23.0%) patients taking statins before the use of iodinated contrast agents, and the person-time incidence rate of in-hospital AKI was 2.5 per 1 000 person-days. The person-time incidence rate of statin users and statin non-users was 3.2 and 2.4 per 1 000 person-days, respectively. Compared with the non-statin group, age, serum creatinine and the proportions of males, admitted to the intensive care unit, lipid metabolism disorder, hypertension, diabetes, cerebrovascular diseases, cardiovascular diseases, using renin-angiotensin- aldosterone inhibitors, using diuretics, using non-steroidal anti-inflammatory drugs, using proton pump inhibitors, iodinated contrast administration via artery, eGFR<60 ml·min -1·(1.73 m 2) -1 were higher, while the proportions of general anesthesia surgery, severe liver diseases and tumors, and eGFR were lower in the statin group (all P<0.05). Among 10 321 patients, 5 867 patients had serum creatinine measurement within 72 hours after iodinated contrast administration, among which 70 patients (4.0 per 1 000 person-days) developed PC-AKI. Multivariate Cox regression analysis showed that statin use was an independent protective factor for in-hospital AKI ( HR=0.65, 95% CI 0.45?0.93, P=0.017) and PC-AKI ( HR=0.44, 95% CI 0.22?0.88, P=0.020). Subgroup analysis showed the significant interaction between diabetes and statin use ( P for interaction=0.039), and the protective effect of statins against in-hospital AKI was only observed in non-diabetic group ( HR=0.45, 95% CI 0.26?0.77). There were no significant differences in subgroups stratified by age, sex, baseline eGFR and the injection method of contrast (all P for interaction>0.05). Conclusions:Statin use prior to iodinated contrast administration is correlated with reduced risks of in-hospital AKI and PC-AKI in hospitalized patients, and the correlation between statin use and in-hospital AKI is more significant in non-diabetic patients. It is suggested that statin use before the application of iodinated contrast agents in hospitalized patients may prevent the occurrence of AKI.

Objective:To determine the correlation between serum soluble CD146 (sCD146) levels and disease activity in patients with systemic vasculitis and the potential of sCD146 as a novel biomarker.Methods:We recruited 304 patients from the systemic vasculitis cohort at Peking Union Medical College Hospital from July 2013 to December 2022. The cohort comprised 200 patients with Takayasu arteritis (TAK) and 104 with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The patient′s demographic and clinical data, including age, sex, disease duration, disease type, laboratory results, and disease status, were extracted from the database. The serum sCD146 concentration was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as mean±standard deviation if normally distributed, with between-group comparisons conducted using the t-test. For non-normally distributed data, median ( Q1, Q3) was used, and comparisons between groups were performed using the Mann-Whitney U test. Categorical data were expressed as percentages, and comparisons between groups were conducted using the Chi-square test or Fisher′s exact test,as appropriate. Kendall′s tau-b′s rank correlation coefficient was calculated to evaluate the correlation between sCD146 and variables associated with systemic vasculitis. A two-sided P value <0.05 was considered statistically significant. Results:Serum sCD146 levels were significantly lower in patients with active disease compared to those in remission in both cohorts [TAK: 246 (218, 287) vs. 277 (230, 322) μg/L, Z=-2.58, P=0.010; AAV: (301±90) vs. (344±81) μg/L, t=-2.56, P=0.007]. Serum sCD146 levels were positively correlated with age and disease duration (TAK: τ=0.09, 0.12, P=0.040, P=0.009; AAV: τ=0.28, 0.15, P<0.001, P=0.020). In patients with TAK, sCD146 levels were negatively correlated with IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity status ( τ=-0.17, -0.18, -0.16, -0.16; P=0.001, P<0.001, P=0.003, P=0.010). In patients with AAV, sCD146 levels were negatively correlated with platelet count (PLT),disease activity status,and the Birmingham Vasculitis Activity Score ( τ=-0.36, -0.27, -0.27; P<0.001, P=0.007, P=0.001). Conclusion:Serum sCD146 levels were significantly lower in patients with active systemic vasculitis than in remission, displaying a negative correlation with disease activity. These findings suggest that sCD146 has potential as a novel biomarker for assessing disease activity in systemic vasculitis.

The pain-evoked potential electroencephalogram (EEG) is an effective electrophysiological indicator for pain assessment, yet its extraction is challenging due to interference from background activity and involuntary blinks. Although existing blink artifact-removal methods show efficacy, they face limitations such as the need for reference signals, neglect of individual differences, and reliance on user input, hindering their practical application in clinical pain assessments. In this paper, we propose a novel framework applying adaptive quadrature mirror filter banks (AQMFB) with discrete wavelet transform (DWT) to remove blink artifacts in pain EEG. Unlike traditional DWT methods that apply fixed wavelets across subjects, our method adapts wavelet construction based on the characteristics of EEG. Experimental results demonstrate that AQMFB-DWT outperforms four leading methods in removing blink artifacts with minimal distortion of pain information, all within an acceptable processing time. This technique is a valuable preprocessing step for enhancing the extraction of pain-evoked potentials.
Humans ; Artifacts ; Blinking/physiology* ; Electroencephalography/methods* ; Pain/diagnosis* ; Male ; Wavelet Analysis ; Adult ; Female ; Evoked Potentials/physiology* ; Young Adult ; Brain/physiopathology* ; Pain Measurement/methods* ; Signal Processing, Computer-Assisted

This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P＜0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P＜0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P＜0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P＜0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P＜0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P＜0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P＜0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P＜0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.