BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.

Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.

Objective:To investigate the clinical features, risk factors, treatment and prognosis of dermatomyositis (DM) patients with positive anti-melanoma differentiation associated gene 5(MDA5) antibody with rapidly progressive interstitial lung disease (RPILD).Methods:The clinical data of 88 DM patients from June 2019 to June 2020, at the rheumatology department of Guangdong Provincial People's Hospital were collected and retrospectively analyzed. T-test, non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and Logistics regression analysis were used for data analysis. Results:① 37%(36/88) DM patients were positive for anti-MDA5 antibody. The frequency of ulcerative rash, Gottron's sign, arthritis, clinically amyopathic dermatomyositis (CADM), and erythrocyte sedimentation rate (ESR) was significantly higher in patients with anti-MDA5 antibody ( P<0.05). The cell count of white blood cell, neutrophil, lymphocyte, and serum creatine kinase (CK) level were significantly lower in the anti-MDA5 antibody positive group than those in the negative group ( P<0.05). Of anti-MDA5 antibody positive DM patients, 100% developed ILD, 34% (11/32)developed RP-ILD, 16%(5/32) died, which were significantly higher than those of anti-MDA5 antibody negative patients ( P<0.05). ② Of anti-MDA5 antibody positive DM patients, the C reactive protein (CRP) level, positive rate of anti-Ro-52 antibody and mortality rate were significantly higher RPILD group than those in the non-RPILD group [15.70(4.49, 29.00) vs 3.22 (1.66, 7.15), Z=-2.440, P=0.014; 91% vs 43%, P=0.011; 46% vs 0, P=0.002]. Logistics regression analysis indicated that positive anti-Ro-52 antibody [ OR=4.561, 95% CI (1.797, 11.580), P=0.001] might be a risk factor for anti-MDA5 antibody positive DM-RPILD. ③ Among patients with anti-MDA5 antibody with RPILD, serum ferritin and D-dimer level was significantly higher and oxygenation index was significantly lower in the non-survival group than those in the survival group [1 931 (1 377, 7 379) vs 638(196, 876), Z=-2.556, P=0.009; 2 760(1 995, 4 854) vs 985(533, 1 588), Z=-2.379, P=0.017; 230(140, 256) vs 309(262, 382), Z=2.191, P=0.030]. In addition, the delayed intensive treatment time was significantly longer in the non-survival group than those in the survival group [(14.0±2.6) vs (4.5±1.4), t=7.899, P<0.01]. Furthermore, the proportion of combined therapy with two disease modifying antirheumatic drug (DMARDs) was significantly lower in the non-survival group than those in the survival group (0 vs 83%, P=0.015). Conclusion:Anti-MDA5 antibody may be associ-ated with characteristic clinical manifestations of DM, ILD, RPILD and high mortality rate. Positive anti-Ro-52 antibody may be a risk factor for anti-MDA5 antibody positive DM-RPILD. High serum ferritin and D-dimer level and low oxygenation index in RPILD patients may be associated with poor prognosis. Early treatment with two DMARDs may improve the prognosis of RPILD.

Objective:To explore the clinical characteristics and early diagnosis of cerebral infarction in critically ill children.Methods:The clinical data of the children who were diagnosed with cerebral infarction in PICU at Shengjing Hospital of China Medical University from January 2013 to September 2019 were analyzed retrospectively.Results:There were 27 children in this study, including 15 males and 12 females.The age of onset ranged from 1 month to 13 years old, with age of 3.0(0.7, 8.0) years old.Among 27 cases, there were ten cases of infection(37.0%), six cases of trauma(22.2%), three cases of congenital heart disease (11.1%), two cases of cerebrovascular disease (7.4%), one case of diabetic ketoacidosis(3.7%) and two cases of autoimmune factors(7.4%). The cause was unknown in three cases(11.1%). The main clinical manifestations were convulsion in 11 cases(40.7%), status convulsion in five cases(18.6%), limb dysfunction in four cases(14.8%), disturbance of consciousness in fvie cases(18.5%) and facial paralysis in four cases(14.8%). Among 27 cases, mechanical ventilation was performed in 12 cases (44.4%). The levels of D-dimer in all children were increased in varying degrees.After improvement and discharge, two children developed secondary epileptic sequelae.Head CT examination was performed in 20 cases, of which 11 cases showed definite cerebral infarction, eight cases of temporal lobe lesions and three cases of basal ganglia lesions.MRI+ MRA examination of the head in 27 cases showed that there were cerebral infarction and the infarct area large.Conclusion:The high incidence age of cerebral infarction in critically ill children is infantile.The most common diseases are infection, trauma, congenital heart disease, and the first clinical manifestations are convulsion and coma.Imaging examination showed that a high proportion of children had large area infarction, and the diagnostic effect of MRI is better than that of CT.D-dimer may be helpful for early clinical diagnosis.

With the rapid changes in lifestyle, natural and social environment, the reproductive health status of couples in childbearing age continues to decline, and long-term outcomes of the rapidly increasing offspring conceived by assisted reproductive technology (ART) needs to be evaluated urgently. Therefore, the focus of research now needs to be extended from death and severe diseases to full life cycle and full disease spectrum. In order to meet the demand for such research, we launched the China National Birth Cohort (CNBC) study, an ongoing prospective and longitudinal study aiming to recruit 30 000 families underwent ART and 30 000 families with spontaneous pregnancies. Long-term follow-up programs will be conducted for both spouses and their offspring. Data of couples and their offspring, such as environmental exposure, reproductive history, psychological and behavioral status, will be collected during follow-up. Peripheral blood, urine, umbilical blood, follicular fluid, semen were also collected at different follow-up nodes. Based on high-quality data and biological samples, CNBC will play an extremely important supporting role and have a far-reaching impact on maternal and children's health care and reproductive health in China. This paper is exactly a brief introduction to the construction and basic design of CNBC.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

OBJECTIVE: To analyze the effects of intradermal needling for pain and tear film stability in patients after pterygium excision. METHODS: A total of 76 patients (98 affected eyes) with primary pterygium were randomly divided into an observation group (38 cases, 53 affected eyes) and a control group (38 cases, 45 affected eyes).In the control group, only pterygium resection was performed, in the observation group, intradermal needling after pterygium resection was applied at Cuanzhu (BL 2), Yuyao (EX-HN 4), Taiyang (EX-HN 5), Sibai (ST 2), Hegu (LI 4), removed after 24 h and changed three times a week. The pain level of 3 days after surgery, dry eye symptoms, the basic tear secretion test (Schirmer-Ⅰ), and the tear-break time (BUT) changes before surgery, 2 weeks after surgery and 4 weeks after surgery were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: The pain level of 3 days after surgery in the observation group was significantly lower than that in the control group (<0.05). The dry eye symptom scores at 2 weeks and 4 weeks after surgery in the two groups were significantly lower than those before surgery (all <0.05), and the dry eye symptom scores in the observation group were significantly lower than those in the control group (both <0.05). The Schirmer-Ⅰ test at 2 weeks and 4 weeks after surgery was significantly prolonged than that before surgery(all <0.05), and the Schirmer-Ⅰ test in the observation group was significantly longer than that in the control group (both <0.05). The BUT at 2 weeks and 4 weeks after surgery in the two groups was significantly longer than that before surgery (all <0.05), and the BUT in the observation group was significantly longer than that in the control group (both <0.05). The total effective rate in the observation group was 89.5% (34/38), which was higher than 71.1% (27/38) in the control group (<0.05). CONCLUSION Intradermal needling can effectively reduce the pain level of patients after pterygium resection, improve dry eye symptoms, promote the secretion of tears and improve the tear film stability.
Acupuncture Points ; Dry Eye Syndromes ; Humans ; Pain ; Pterygium ; Tears

Objective To investigate the high risk factors of new dysfunction in Pediatric Intensive Care Unit.Methods A retrospective cohort case control analysis was performed in order to investigate the 906 patients admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from January 2015 to January 2016.Assessment of Functional Status Scale(FSS) was performed at both admission and discharge.According to the new dysfunction diagnostic criteria,all cases were divided into new dysfunction group and control group.The 2 groups were compared in gender,glucocorticoids application time,mechanical ventilation application time,sedation application time,neuromuscular blockers application time,albumin,alanine aminotransferase,aspartate aminotransferase,creatine kinase,creatine kinase isoenzyme,leukocyte,hemoglobin and C-reactive protein.Multivariate Logistic regression was used to screen the risk factors leading to new dysfunction.All cases were divided into high risk factors group and control group according to the risk factors.The 2 groups were compared in initial FSS,FSS of discharge,ΔFSS and the discharge FSS of mental status domain,FSS of sensory domain,FSS of communication domain,FSS of motor domain,FSS of feeding domain,and FSS of respiratory domain.Results Among the 906 cases,547 cases were male and 359 cases were female,and average age was (28.1-± 1.9) months.There were 81 cases in new dysfunction group and 825 cases in control group.Factors such as mechanical ventilation application time [(3.7 ±-0.5) d vs.(1.1 ±-0.1) d],glucocorticoid application time [(3.2-±0.6) d vs.(1.7-±0.1) d],sedation application time[(4.7 ±0.7) d vs.(1.7 ±0.1)d],neuromuscular blockers application time [(0.7 ± 0.3) d vs.(0.1 ± 0.03) d],albumin [(35.6 ± 0.8) g/L vs.(40.5 ± 0.2) g/L],creatine kinase isoenzyme [(75.8 ± 12.4) U/L vs.(49.7 ± 2.6) U/L] had significant differences between the new dysfunction group and the control group(all P ＜ 0.05).Multivariate Logistic regression analysis revealed that more than 7 days of mechanical ventilation,more than 7 days of glucocorticoids application,more than 7 days of sedation application,hypoalbuminemia were risk factors to develop new dysfunction [OR =0.69 (95％ CI:0.62-0.78),OR=0.62 (95％ CI:0.75-0.94),0R=0.75 (95％ CI:0.68-0.84),0R=0.68 (95％ CI:1.06-1.16),all P ＜0.05].In the more than 7 days of mechanical ventilation group,FSS at discharge,FSS of mental status,FSS of sensory,FSS of communication,FSS of motor,FSS of feeding,FSS of respiratory were significantly different from those of the mechanical ventilation application time ≤ 7 d group (all P ＜ 0.05).In the more than 7 days of glucocorticoids application group,FSS of mental status,FSS of sensory,FSS of communication were significantly different from those of the glucocorticoids application time ≤7 d group (all P ＜ 0.05).In the more than 7 days of sedation application group,FSS at discharge,FSS of mental status,FSS of sensory,FSS of communication,FSS of motor were significantly different from those of the sedation application time ≤7 d group(all P ＜ 0.05).Concltsion More than 7 days of mechanical ventilation,glucocorticoids application and sedation application not only increase the incidence of new dysfunction,but also affect mental,sensory,communication,motor function,the muscle and cognitive function at discharge and prognosis.

Objective To investigate the imaging features of the calvarial cavernous hemangioma and the surgical efficacy to improve diagnosis and treatment of the calvarial cavernous hemangioma.Methods The clinical information,imaging materials and surgical efficacy from ten cases of calvarial cavernous hemangioma confirmed by pathology and the related literature was reviewed.Results The lesion was located in frontal bone in eight cases,in parietal bone in one case and in occipital bone in one case.The lesions were round-shape hypodensity with clear margin in X-ray.The lesions were hyperdensity or slightly hyperdensity on CT scan,and were osteolytic lesions with a characteristic honeycomb or starburst pattern on bone window.The MRI features were complicated and variable.The lesions were heterogenous and unevenly enhanced signal intensity.Nine patients underwent radical resections and reconstructed immediately by titanium mesh.The patient with tumor in occipital bone underwent radical resection only.Macroscopically,the pathologic bone was a huge purple-red blush mass protruding from the skull surface.Histological examination revealed the diploe with large,thin-walled,dilated blood-filled spaces lined by flattened endothelial cells without evidence of malignancy.No recurrence was noted in any case during a follow-up period from 3 to 24 months.All the patients survived well without recurrence.Conclusions The imaging features of calvarial cavernous hemangioma have a high value in the diagnosis and may provide guidance for the treatment.The radical resection and immediate reconstruction treatment for calvarial cavernous hemangioma is satisfied.

Objective To investigate the diagnostic value of plasma B-type natriuretic peptide(BNP) in left to right shunt congenital heart disease accompanied by heart failure in PICU.Methods We retrospectively reviewed the clinical data of 52 cases diagnosed left to right shunt congenital heart disease in the PICU of Shengjing Hospital of China Medical University from January 2012 to June 2014.The cases were divided into negative control group(n=18) and heart failure group(n=34) according to the criteria for the diagnosis of pediatric heart failure.We respectively compared plasma BNP,size of heart defects,left ventricular end-diastolic volume index(LVEDVI),ratio of left ventricular early diastolic filling blood flow velocity and left ventricular late diastolic filling blood flow velocity(E/A),left ventricular ejection fraction(LVEF),pulmonary artery systolic pressure(PASP),and cardiothoracic ratio between the two groups.We analyzed the correlation between plasma BNP and the size of heart defects,LVEDVI,E/A,cardiothoracic ratio,LVEF,PASP.The receiver operating characteristic curve was used to determine the optimal cut-off value of plasma BNP to diagnose heart failure.Results Plasma BNP were 87.7(22.7,165.7)pg/ml in negative control group and 716.5(326.8,1813.0)pg/ml in heart failure group.The plasma BNP level of heart failure group was significantly higher than that of negative control group(Z=5.3,P<0.01).Size of heart defects were 5.0(3.0,6.8) mm in negative control group and 7.4(5.5,9.0)mm in heart failure group.Size of heart defects of heart failure group was significantly higher than that of negative control group(Z=3.5,P<0.01).LVEDVI were (44.6±18.3)ml/m3 in negative control group and (70.8±38.4)ml/m3 in heart failure group.LVEDVI of heart failure group was significantly higher than that of negative control group(t=2.7,P=0.01).E/A were 1.3±0.3 in negative control group and 1.1±0.3 in heart failure group.E/A of negative control group was significantly higher than that of heart failure group(t=2.2,P=0.04).Plasma BNP had a positive relation with cardiothoracic ratio(r=0.49,P=0.01) and a negative correlation with E/A(r=-0.28,P=0.04).The optimal cut-off value of plasma BNP was 181.8 pg/ml.The sensitivity of diagnosis of heart failure was 94% and the specificity was 88%.The area under the receiver operating characteristic curve was 0.951.Conclusion Plasma BNP may comprise a sensitive marker for heart failure of left to right shunt congenital heart disease.It is recommended that 181.8 pg/ml is the optimal cut-off value to diagnose heart failure of left to right shunt congenital heart disease.