BACKGROUND:Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis,and Hemin can regulate the expression of mitochondria-related proteins. OBJECTIVE:To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS:(1)In vitro cell experiment:Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis.The optimal concentration of Hemin(0,1,10,20,40,80,and 160 μmol/L)for the intervention in mouse chondrocytes was determined by cell counting kit-8 method.Chondrocytes were randomly divided into control group,model group(interleukin-1β)and Hemin group(interleukin-1β+Hemin).Reactive oxygen species,mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected.(2)In vivo experiment:Adult C57BL/6 mice were randomly divided into normal group,model group(osteoarthritis)and Hemin group(osteoarthritis+Hemin),with eight mice in each group.After 4 weeks of Hemin treatment,the behavioral test and histopathological observation of the knee joint were performed in each group.Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION:In vitro experiment:the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L.Compared with the model group,the level of reactive oxygen species was significantly reduced,the mitochondrial membrane potential was significantly improved,and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes.In vivo experiment:After 4 weeks of treatment,compared with the model group,the lower limb function of mice in the Hemin group was significantly improved,the histopathological score was significantly improved,and the apoptosis of knee chondrocytes was significantly reduced.All these findings indicate that Hemin can alleviate oxidative stress,restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β.Hemin can improve extracellular matrix degradation,promote chondrocyte anabolism,reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis.It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To observe the value of high-frequency ultrasound(HFUS)and shear wave elastography(SWE)parameters of lower extremity muscles for evaluating dermatomyositis(DM).Methods Totally 19 DM patients(DM group)and 20 healthy subjects(control group)were prospectively enrolled,and lower extremity muscles HFUS and SWE examinations were performed.The echoes,thickness and shear wave velocity(SWV)of bilateral vastus lateralis and lateral head of gastrocnemius were compared between groups.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each ultrasonic parameter for evaluating DM.Results The proportion of muscle echo score of 1-point,thickness of bilateral lateral head of gastrocnemius,SWV of bilateral vastus lateralis and lateral head of gastrocnemius in DM group were all lower than those in control group(all P＜0.05).SWV of bilateral vastus lateralis and left lateral head of gastrocnemius had excellent efficacies for evaluating DM(AUC 0.932-0.968).The thickness of bilateral lateral head of gastrocnemius and SWV of right lateral head of gastrocnemius had good efficacy for evaluating DM(AUC 0.784-0.884),while the muscles'echo had general efficacy(AUC=0.658).Conclusion HFUS and SWE parameters of lower extremity muscles could be used to evaluate DM,among which SWE parameters had relatively higher values.

Objective:To study the growth trajectory and the incidence of malnutrition and clinical events in infants with congenital heart disease in 1 year after surgery.Methods:Children at the age of 1 year or younger who were diagnosed with congenital heart disease and underwent surgery at Guangzhou Women and Children's Medical Center affiliated to Guangzhou Medical University from January 2018 to January 2019 were included. The age, gender, birth weight and length, and parental height and weight were collected, and the occurrence of clinical events of interest and the children's health as evaluated by caregiver within 1 year after surgery were followed up through questionnaire survey. Malnutrition was defined as a weight-for-age z-score (WAZ) ≤-2 at 1 year after surgery and a WAZ>-2 was defined as non-malnourished.Results:Among the 502 children, 301 were boys and 201 were girls, aged 4.1 (range: 2.0 to 6.8) months, of whom 64.7% were with simple congenital heart disease and 35.3% complex congenital heart disease. The children were generally with mild malnutrition (WAZ<-1 and >-2) before surgery. At 3 months and 6 months after surgery, the children showed a rapid growth catch-up, although failing to reach the normal level, and the trend plateaued at 1 year after surgery. The proportion of children with malnutrition decreased gradually within 1 year after surgery. 47.0% of included children had malnutrition before surgery, and the proportion decreased significantly at 3 months and 6 months, to 17.9% at 1 year after surgery. After discharge, these children suffered from upper respiratory infection most commonly (74.5%), followed by pneumonia (41.2%) and diarrhea (36.7%), and vomiting and constipation (22.1%). In terms of children's health status as evaluated by parents, about 32.0% of families considered their children in poor health before surgery, and the proportion decreased to 6.9% within 1 year after surgery.Conclusion:Infants with congenital heart disease continued to grow and catch up within 1 year after surgery, showing significantly improved nutrition status, but some children still experienced malnutrition at 1 year after surgery.

Objective To compare the effects of ginsenosides Rg1 and Rb1 on depression-and anxiety-like behaviors in chronic unpredictable stress-induced rats.Methods Seventy male SPF grade SD rats were tested for sugar and water preference after 5 days of adaptation and divided into seven groups according to their preference index:a control group,model group,fluoxetine hydrochloride group,ginsenoside Rg1 24 mg/kg group,ginsenoside Rg1 48 mg/kg group,ginsenoside Rb1 33 mg/kg group,and ginsenoside Rb1 67 mg/kg group.All rats,except for the control group,were subjected randomly to one or two different stimulating factors every day for a total of 35 days.On the 36th day,behavioral experiments including sugar and water preference,open field,novel environment feeding inhibition,elevated cross maze,and forced swimming experiments were conducted to investigate the anti-depression and anti-anxiety effects of the treatments.Serum and hippocampal levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α and serum corticosterone were measured by enzyme-linked immunosorbent assay.Results Compared with the model group,ginsenoside Rg1 and Rb1 significantly increased sucrose consumption in the sucrose preference test and decreased immobility in the forced swimming test.Ginsenoside Rg1(48 mg/kg)significantly reduced the latency to eat in the novelty-suppressed feeding test,and ginsenoside Rg1(24 and 48 mg/kg)significantly increased the percentage of open arm entries and time in the elevated cross maze test.Serum corticosterone levels were significantly decreased in the ginsenoside Rg1 and Rb1 groups,serum IL-1β and IL-6 levels were significantly decreased in the ginsenoside Rg1(48 mg/kg)group,serum TNF-α and IL-6 levels were significantly decreased in the ginsenoside Rb1(33 mg/kg)group,and IL-1β,IL-6,and TNF-α levels in the hippocampus were significantly decreased in the ginsenoside Rg1(48 mg/kg)and Rb1(67 mg/kg)groups.Conclusions Both ginsenosides can regulate the hypothalamic-pituitary-adrenal axis and inhibit neuroinflammation,improving depression-and anxiety-like behaviors in rats induced by chronic unpredictable stress.Ginsenoside Rg1 has a significantly better anti-anxiety effect than Rb1.

Objective:To evaluate the role of mitochondria-associated endoplasmic reticulum membranes (MAMs) regulated by protein tyrosine phosphatase interacting protein 51 (PTPIP51) in sevoflurane-induced necroptosis in hippocampal neurons of rats using the in vitro experiment.Methods:Primary cultured hippocampal neurons from fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well ) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 4 groups ( n=19 each) using a random number table method: control group (C group), sevoflurane group (Sev group), sevoflurane+ siRNA-PTPIP51 transfection group (Sev+ siPTPIP51 group), and sevoflurane+ nonsense siRNA transfection group (Sev+ siNC group). The neurons were placed in a culture incubator containing 2% sevoflurane and incubated at 37 ℃ for 5 h in Sev, Sev+ siPTPIP51 and Sev+ siNC groups. Then neurons were collected for determination of the cell survival rate (by MTT method), cytoplasmic calcium concentration ([Ca 2+ ] i) and necroptosis rate (by flow cytometry), expression of PTPIP51, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) (by Western blot) and for microscopic examination of the partial length, endoplasmic reticulum circumference, and mitochondrial circumference of MAMs (with a transmission electron microscope). Results:Compared with group C, the activity of neurons was significantly decreased, the [Ca 2+ ] i and necroptosis rate were increased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were increased in group Sev ( P<0.05). Compared with group Sev, the activity of neurons was significantly increased, the [Ca 2+ ] i and necroptosis rate were decreased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were decreased in group Sev+ siPTPIP51 ( P<0.05), and no statistically significant changes were found in the above parameters in group Sev+ siNC ( P>0.05). Conclusions:Up-regulation of PTPIP51 expression mediates structural changes in MAMs and is involved in the process of sevoflurane-induced necroptosis in hippocampal neurons of rats.

Objective:To explore the mediating effect of carotid atherosclerosis on serum triglyceride-glucose (TyG) index and silent lacunar infarction (SLI) in non-diabetic population.Methods:A total of 2 482 patients were selected from the Health Examination Center of Hebei General Hospital from January 2019 to December 2021. The basic demographic information, biochemical parameters, calculated TyG index and carotid plaque score were collected. SLI was diagnosed according to the criteria formulated by Chinese Society of Neurology. Participants were divided into SLI group and non-SLI group according to whether there was SLI in brain magnetic resonance imaging, and the non-SLI group was normal without lacunar infarction. Spearman correlation analysis was used to explore the correlation between TyG index and carotid plaque score. Binary Logistic regression analysis was used to analyze the effects of TyG index and carotid plaque score on SLI. Bootstrap was used to explore whether carotid plaque score mediated the association between TyG index and SLI.Results:There were 471 patients (18.98%) who had SLI, and 2 011 patients (81.02%) did not. Carotid plaque score [2(0, 5) vs 1(0, 3)] and TyG index [7.17(6.81, 7.64) vs 7.12(6.77, 7.54)] were increased in the SLI group compared with the non-SLI group ( Z=-4.213, Z=-2.636, P<0.05). Spearman correlation analysis showed that carotid plaque score was positively correlated with TyG index ( r=0.083, P<0.001). Multivariate Logistic regression analysis indicated that carotid plaque score ( OR=1.047, 95% CI 1.002-1.094) and TyG index ( OR=1.329, 95% CI 1.106-1.598) were independent risk factors for SLI ( P<0.05). Mediated effect analysis showed that TyG index had a direct effect on the incidence of SLI (β=0.265, 95% CI 0.102-0.428). Carotid plaque score partially mediated the effect of TyG index on the incidence of SLI (β=0.024, 95% CI 0.009-0.043), and the mediating effect accounted for 8.30% of the total effects. Conclusion:In non-diabetic population, TyG index and carotid plaque score are predictors of SLI, and the carotid plaque score is a partial mediator in the effect of TyG index on the incidence of SLI.

Objective To investigate the effect of cornus officinalis glycosides on apoptosis and oxidative damage of human renal tubular epithelial cells line induced by high glucose by regulating E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods Human renal tubule epithelial cell line HK-2 was divided into control group(control,5.5 mmol/L glucose),model group(HG,30 mmol/L glucose),and total cornus offici-nalis glycosides groups with low,medium and high dose(L-COG,M-COG,H-COG).After Nrf2 pathway inhibitors were added,HK-2 cells were divided into H-COG group and ML385 group.CCK8 method was used to detect cell activity.Apoptosis was detected by flow cytometry.The expressions of Bcl-2 associated X protein(Bax),B-cell lymphoma/leukemia 2(Bcl-2),activated caspase3(cleaved caspase3),Nrf2/HO-1 pathway protein were detected by Western blot.Reactive oxygen species(ROS)content was detected by DCFH-DA,glutathione peroxi-dase(GSH-Px)activity,superoxide dismutase(SOD)activity,interleukin-6(IL-6)content and tumor necrosis factor α(TNF-α)content were detected by ELISA.Results Compared with control group,the cell activity,Bcl-2 protein expression,GSH-Px and SOD activity in model group were significantly decreased,and the apoptosis rate,Bax,Nrf2,HO-1 and cleaved caspase3 protein expression,ROS,IL-6 and TNF-α content were significantly in-creased(P＜0.05).Compared with model group,the cell activity,Bcl-2 protein expression,GSH-Px and SOD ac-tivity of L-COG,M-COG,and H-COG were significantly increased.Apoptosis rate,Bax,Nrf2,HO-1,cleave-caspase3 protein expression,ROS,IL-6,TNF-α content were significantly decreased(P＜0.05).Compared with H-COG,the cell activity,Bcl-2 protein expression,GSH-Px and SOD activity in ML385 group were significantly increased.The apoptosis rate,Bax and cleaved caspase3 protein expression,ROS,IL-6,TNF-α content were sig-nificantly decreased(P＜0.05).Conclusions The total cornus officinis glucoside may reduce the oxidative stress and inflammatory response of renal tubular epithelial cells induced by high glucose through inhibiting Nrf2/HO-1 pathway and then reduce cell apoptosis.