Epilepsy is a chronic neurological disease characterized by abnormal synchronous discharges of brain neurons. The mutation of GRIN1， a key gene encoding the essential GluN1 subunit of N-methyl-D-aspartate （NMDA） receptors， is closely associated with the pathogenesis and progression of epilepsy. This review summarizes research advances in GRIN1 mutation-related epilepsy， with a focus on its molecular mechanisms， clinical phenotypes， factors influencing phenotypic heterogeneity， and treatment strategies. In terms of molecular mechanisms， GRIN1 mutations affect NMDA receptor function through gain-of-function and loss-of-function mechanisms. Clinical phenotypes show significant heterogeneity， including seizure types， age of onset， and comorbid neurodevelopmental disorders. This heterogeneity may be related to the domain where the mutation is located， the mutation type， and the degree of impact on receptor function. Regarding treatment， gain-of-function mutations can be managed with NMDA receptor antagonists， while loss-of-function mutations may be treated with positive allosteric modulators. The ketogenic diet has also demonstrated potential therapeutic effects. This review aims to provide references for basic research and clinical translation in GRIN1 mutation-related epilepsy， and to promote the development of precision diagnosis and treatment.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

BackgroundThe professional self-concept of nurses is a crucial indicator for their personal growth， development and career planning. Previous studies have shown that work stressors during the internship period may lead to a decrease in the level of professional self-concept among nursing students. Given the existing differences in social roles between nursing students and clinical nurses， the influencing factors of professional self-concept in clinical nurses and its relationship with work stressors require further research. ObjectiveTo explore the relationship between work stressors and professional self-concept among nurses， so as to provide references for improving the level of professional self-concept of clinical nurses. MethodsFrom December 2022 to February 2023， a stratified random sampling method was employed to select 260 in-service nurses from Mianyang Hospital of Traditional Chinese Medicine as the study subjects. Chinese Nurses Stressor Scale （CNSS） and Professional Self-concept of Nurses Instrument （PSCNI） were used for assessment. Pearson correlation analysis was conducted to examine the correlation between CNSS scores and PSCNI scores of nurses. Multiple linear regression analysis was utilized to explore the factors influencing the professional self-concept of nurses. ResultsA total of 238 nurses （91.54%） completed valid questionnaires. PSCNI total score yielded a statistical difference among nurses with different marital statuses （F=8.947， P<0.05）. PSCNI total scores were significantly higher in nurses with emergency medical service experience than those without such experience （t=2.208， P<0.05）， and were significantly lower in nurses with abnormal physical examination findings in the past year than those without abnormal findings （t=-2.584， P<0.05）. Correlation analysis revealed that CNSS total score and subscale scores were negatively correlated with PSCNI total score （r=-0.275~-0.169， P<0.01）. Multiple linear regression analysis indicated that work expectation-related stressors， marital status and emergency medical service experience might be influencing factors of their professional self-concept （β=-0.350， 0.345， 0.183， P<0.01）. ConclusionNurses' work stressors are closely correlated with their professional self-concept， and high levels of stressors related to nurses' expectations may lead to a decrease in their professional self-concept levels. ［Funded by 2021 Research Project of Mianyang Municipal Health Commission （number， 202154）］

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

Objective To explore the comparative application of phase and diaphragmatic navigation in three-dimensional magnetic resonance cholangiopancreatography(3D-MRCP)thin-layer scanning in elderly patients.Methods A total of 180 elderly patients were scanned by phase and diaphragmatic navigation via Siemens Aera1.5T superconducting MR scanner.The acquired images were reconstructed by 3D reconstruction.The anatomical structure,image quality and disease diagnosis were compared between the phase and diaphragmatic navigation groups.Results In liver of anatomy,the liver of primary bile duct,the superior,middle and inferior extrahepatic bile duct and the gallbladder could be well displayed,and the difference was not statistically significant between the two groups(P＞0.05).The display of pancreatic duct and the liver of secondary bile duct of diaphragmatic navigation was significantly better than those of phase navigation(P＜0.05).In terms of image quality,the excellent rate of diaphragmatic navigation was significantly higher than that of phase navigation,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the detection rate of pancreatobiliary system diseases,the diagnostic rate of cholelithiasis,common bile duct stones,common bile duct dilatation and pancreatic duct dilatation between the two groups(P＞0.05).Conclusion Diaphragmatic navigation is signifi-cantly better than phase navigation in the display of the anatomical structure of the pancreatic duct,the liver of secondary bile duct,and the excellent rate of image quality.Diaphragmatic navigation is more suitable for thin-layer 3D-MRCP scanning in elderly patients.

Secretogranin Ⅲ (SCG3) is a kind of secretory granule widely distributed in tissues and cells with endocrine functions in the human body.As a member of the granin family, it is generally considered to be involved in endocrine and neuroendocrine regulatory activities, and also as a highly disease-selective angiogenic factor that reduces vascular leakage and neovascularization in animal models of diabetic retinopathy and retinopathy of prematurity.In addition, SCG3 also co-expresses with inflammatory factors, anti-brain-derived neurotrophic factors in nerve cells.This article reviewed the current understanding of SCG3 as a secretory granular protein and its granulocyte family, analyzed the distribution of SCG3 in vivo, discussed its role in angiogenesis, and considered the correlation between SCG3 and neovascularization.It focused on the possible role and significance of SCG3 in diabetic retinopathy, especially in relation to microangiopathy, inflammatory factors and retinal neurodegeneration.By comparing the differences between SCG3 and vascular endothelial growth factor (VEGF) in the binding of signaling pathways and related receptors, the effects and advantages of anti-SCG3 drugs in the treatment of DR were prospected.

BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

Objective To explore the effect of MSCT 3D scanning and reconstruction on developmental dysplasia of the hip(DDH)in adult patients with total hip arthroplasty,The predictive value of acetabular prosthesis selection and osteotomy accuracy in THA.Methods Selection in our hospital between February 2021 and February 2023 were 60 adult DDH patients underwent total hip replacement,which USES routine preoperative planning as a control group of 30 patients,and using MSCT + reconstruction of 3 d scanning technology as observation group of 30 patients,planning after the completion of the planning of the surgical operation and implant placement,Relevant information was collected before and after the operation of the two groups.Operation time,intraoperative blood loss,intraoperative fluoroscopy time,acetabular prosthesis selection and matching rate,femur split fracture rate,pelvis and acetabular reduction quality,Majeed score and Harris hip function score were compared between the two groups.The osteotomy distance and sharp shoulder distance of the two groups were compared before planning and in actual conditions,and the correlation between MSCT 3D scanning and reconstruction technology and the accuracy of acetabular prosthesis selection was evaluated.Results Results analysis showed that MSCT 3D scanning+reconstruc-tion technology used in preoperative evaluation of patients in the observation group was correlated with the accuracy of acetabular prosthesis selection(P＜0.05),and the absolute errors of osteotomy distance and sharp shoulder distance of patients in the observation group were smaller than the actual situation before planning(P＜0.05).In addition,compared with the control group,the operative time,intraoperative blood loss,intraoperative fluoroscopy time and incidence of femoral split fracture in the observation group were significantly lower,and the matching rate of acetabular prosthesis selection,the Majeed scores and Harris scores were significantly higher in the following 3 months were significantly higher(P＜0.05).The reduction quality of pelvis and acetabulum was not statistically significant between the two groups(P＞0.05).Conclusion Msct-based 3D scanning + reconstruction has a high predictive value for the selection of acetabular prosthesis and the accuracy of osteotomy in adult DDH total hip replacement,and the use of this technology for preoperative planning has a significant optimization effect on the actual treatment effect and patient recovery.

Objective:To investigate the effect of oxygen-driven nebulization inhalation combined with invasive mechanical ventilation on sputum viscosity and inflammatory indicators in patients with severe pneumonia complicated by respiratory failure.Methods:A total of 300 patients with severe pneumonia complicated by respiratory failure who received treatment at Lanxi Traditional Chinese Medicine Hospital from June 2021 to June 2023 were included in this prospective study. Using the random number table method, the patients were divided into a control group (conventional invasive mechanical ventilation, n = 150) and a treatment group (conventional invasive mechanical ventilation + oxygen-driven aerosol inhalation, n = 150). The sputum viscosity, inflammatory indicators, and blood gas analysis indicators were compared between the two groups before and after treatment. The occurrence of ventilator-associated pneumonia, mechanical ventilation time, intensive care unit stay duration, and the length of hospital stay were recorded. Results:After treatment, the sputum viscosity grade of the treatment group was significantly different from that of the control group ( Z = 7.09, P < 0.05). The serum levels of interleukin-6 and interleukin-10 in the treatment group were significantly lower, with values of (8.19 ± 0.91) μg/L and (19.26 ± 2.17) μg/L, respectively, compared with (12.01 ± 1.34) μg/L and (32.57 ± 3.85) μg/L in the control group ( t = 28.88, 36.88, both P < 0.05). The arterial partial pressure of oxygen in the treatment group post-treatment was (95.75 ± 3.51) mmHg (1 mmHg = 0.133 kPa), which was significantly higher than (90.14 ± 3.64) mmHg in the control group ( t = 13.58, P < 0.001). The arterial partial pressure of carbon dioxide in the treatment group was (40.65 ± 4.03) mmHg, which was significantly lower than (44.81 ± 4.12) mmHg in the control group ( t = 8.84, P < 0.001). The incidence of ventilator- associated pneumonia in the treatment group was significantly lower than that in the control group ( χ2 = 14.00, P < 0.001). The mechanical ventilation time, intensive care unit stay duration, and the length of hospital stay in the treatment group were significantly shorter compared with the control group ( t = 25.82, 18.23, 15.28, all P < 0.001). Conclusion:Oxygen-driven aerosol inhalation combined with invasive mechanical ventilation can effectively dilute sputum, reduce the patient's inflammatory response, improve blood gas analysis indicators, lower the risk of ventilator- associated pneumonia, and thereby facilitate recovery from severe pneumonia complicated by respiratory failure.