Objective:To systematically evaluate the care experience of family caregivers for amyotrophic lateral sclerosis (ALS) patients, providing guidance for home care of ALS patients.Methods:Qualitative studies on the care experience of family caregivers for ALS patients were retrieved from PubMed, American Psychological Association Psychnet, CINAHL, Web of Science, Medline, Cochrane Library, Embase, China Biology Medicine disc, WanFang Data, VIP, and China National Knowledge Infrastructure. The search period was from database establishment to October 30, 2022. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center (2016 edition). The aggregative integration method was used to integrate the results using NVivo 11 software.Results:A total of 11 studies were included. A total of 22 complete and clear results were extracted and combined to form eight new categories, which were integrated into three results, namely, family caregivers facing personal development limitations and various family difficulties, experiencing complex and chaotic emotional experiences, and craving for diversified care support.Conclusions:Nursing staff should pay attention to the impact of ALS on their patient's family caregivers, provide caregiver knowledge and skill guidance, promote positive emotional experiences, and offer diversified care support to improve the quality of life of patients and family caregivers.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

【Objective】 To explore the application value of different language assessment tools in the assessment of language development of 12-month-old high-risk infants, and to screen out simple and valid language assessment tools. 【Methods】 A total of 217 11- to 13-month-old high-risk infants who were followed up at the outpatient service for high-risk infants at the child health clinic of Guiyang Maternal and Child Health Hospital from March 2022 to May 2023 were selected as the study subjects. Their language was evaluated by Early Language Milestone Scale (ELMS), Putonghua Communicative Development Inventory (PCDI) and Ages and Stages Questionnaire-Third Edition (ASQ-3). With Gesell as the gold standard for the assessment of language, the area under receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, Youden index and Kappa value of the three tools were calculated. Spearman correlation analysis was used to analyze the correlation between the different language assessment scales. The Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was used to evaluate the three tools. 【Results】 1)Among 217 high-risk infants, 78 preterm infants was the most (35.94%). The rate of delayed language development detected by Gesell, ELMS, PCDI-comprehension, PCDI-expression, ASQ-3 were 5.5%, 7.8%, 36.4%, 30.0% and 11.5%, respectively. 2)ASQ-3 had the strongest correlation with Gesell language region (rs=0.607, P<0.01) and it had the most AUC (AUC=0.812, P<0.05). The consistency between ASQ-3 and Gesell was moderate (Kappa=0.56, P<0.01). ASQ-3 had the highest sensitivity(91.7%), accuracy(93.1%), negative predictive value(99.5%) and Youden index(0.85), and ELMS had the highest specificity(94.6%). 3) Comprehensive evaluation of three tools by the TOPSIS indicated that ASQ-3 was the best, followed by ELMS and PCDI-comprehension was the worse. 【Conclusion】 Among the three assessment tools, ASQ-3 has the highest value in assessing the language development of 11- to 13-month-old high risk infants, and it may be necessary to expand the age range and establish a national norm of ELMS and PCDI in the future.

Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Objective:To construct the prediction model of knee degeneration in patients with knee osteoarthritis based on bioelectrical impedance index, and evaluate the prediction performance and application efficiency of the model.Methods:This was a cross-sectional study. From May to July 2021, 248 knee joints of 124 patients with knee osteoarthritis at home from Shijiazhuang Yuqiang Community Health Service Center who participated in physical examination were selected by convenience sampling to establish the model. According to Kellgren-Lawrence (K-L) grading system, the knee joints were divided into four groups, namely K-L1 ( n=19) , K-L2 ( n=103) , K-L3 ( n=96) , and K-L4 ( n=30) . The indicators included in the model were selected through analysis of variance or Kruskal-Wallis test, and a prediction model of knee degeneration was established using support vector machine, and the model was optimized using grid parameter optimization method. The prediction performance of the model was evaluated by the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, accuracy, positive predictive value and negative predictive value. Results:The indicators in the model included age, complications, lumbar/back/hip pain, high-risk occupation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) -pain, WOMAC-function, capacitive reactance and phase angle. The area under the ROC curve of the training set model was 0.999, the prediction accuracy was 0.920, and the 95% confidence interval was 0.868 to 0.957. The area under the ROC curve of the test set model was 0.833, the prediction accuracy was 0.682, and the 95% confidence interval was 0.572 to 0.780.Conclusions:The prediction model of knee degeneration has good prediction performance and is easy to use, which can be used as a screening tool for knee degeneration in patients with knee osteoarthritis.

In this article, methods of measuring and evaluating treatment adherence, based on whether they are objective and subjective, are reviewed upon literature examination, and the advantages and disadvantages of each method for different population segments are also discussed.It is intended to provide medical professionals and researchers with a general framework about adherence assessment methods.During treatment and research, medical professionals and researchers should select the most appropriate methods for their purposes and provide effective and personalized evaluation methods to ultimately evaluate and improve patients' medication adherence.

To summarize the clinical manifestations of a case with 46, XY sex development disorder caused by myelin regulatory factor(MYRF) gene mutation and review the literature to deepen the specialists′ understanding of the clinical disease spectrum resulting from MYRF gene variations. The child had a female phenotype with mild masculinity, chromosome 46, XY, sex-determining region of Y gene(SRY gene) positive, laboratory tests were consistent with primary hypogonadism, ultrasound did not detect the gonads, but the residual reproductive tract was visible, and echocardiography suggested coarctation of the aorta, MYRF gene c. 2518C>T(p.R840*) heterozygous variant. The father did not carry this variant. The mother was untraceable, and genetic testing had not been completed. It was analyzed as pathogenic variation according to American College of Medical Genetics and Genomics(ACMG) guidelines. Sixteen cases of disorders of sex development caused by MYRF gene variation reported from 2018 to 2021 were reviewed, MYRF gene variants, 46, XY, and 46, XX individuals can be pathogenic, can affect the gonad and reproductive tract at the same time, and can also affect multiple systems. In this case, the patient presents with 46, XY sex development disorder due to MYRF gene mutation, accompanied by rare cardiovascular complications. When encountering 46, XY primary hypogonadism without well-developed Müllerian duct structures, this condition should be considered. Following confirmation, a comprehensive assessment of multi-organ function is necessary.

Objective To investigate the impact of usnic acid on neuronal necroptosis in rats with cerebral infarction by regulating the receptor-interacting protein kinase 1(RIPK1)/receptor-interacting protein kinase 3(RIPK3)/mixed lineage kinase domain-like protein(MLKL)signaling pathway.Methods The rat model of cerebral infarction was established by middle cerebral artery occlusion and reperfusion(MCAO/R).The successfully modeled rats were divided into model group,NEC-1(RIP1 inhibitor)group,low-,medium-,and high-dose of usnic acid groups,with 20 rats in each group.Another 20 rats were selected as a sham-operation group.After 3 days of drug intervention,the modified Neurological Severity Scale(mNSS)was applied to evaluate the degree of neurological damage of rats in each group.TTC staining was applied to detect the volume of cerebral infarction.HE staining was selected to observe pathological damage in brain tissue.PI/NeuN staining was selected to observe neuronal necrosis.RT-qPCR was used to detect mRNA levels of RIPK1,RIPK3 and MLKL in rat ischemic brain tissue.Western Blot was used to determine the expressions of RIPK1/RIPK3/MLKL signaling pathway related proteins in rat ischemic brain tissue.Results Compared with the sham-operation group,the neural cells in the model group showed structural damage,cell disrupted,deformation,and nuclear pyknosis,furthermore,the mNSS score,the cerebral infarction volume,proportion of PI-positive neurons were significantly increased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL in brain tissue,ratio of p-RIPK1/RIPK1,and the levels of RIPK3 and MLKL proteins were obviously increased(P＜0.05).Compared with the model group,the damage degree of neurocyte morphology in the low-,medium-,and high-dose of usnic acid groups was gradually alleviated,the nuclear membrane was gradually became clear,and the cell body was gradually returned to normal.The neurocyte morphology in the NEC-1 group was basically intact,and the nuclear membrane was basically clear.The mNSS score,cerebral infarction volume and proportion of PI-positive neurons in NEC-1 group and usnic acid groups were significantly decreased(P＜0.05).The mRNA levels of RIPK1,RIPK3,MLKL,ratio of p-RIPK1/RIPK1,and levels of RIPK3 and MLKL proteins in brain tissue were obviously reduced in usnic acid groups and NEC-1 group.Also,there was dose-dependent decrease in usnic acid groups(P＜0.05).No statistically obvious difference was found between the high-dose usnic acid group and the NEC-1 group(P＞0.05).Conclusion Usnic acid inhibits neuronal necroptosis in rats with cerebral infarction by inhibiting the RIPK1/RIPK3/MLKL signaling pathway,thereby alleviating brain injury in rats with cerebral infarction.

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.