OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective To investigate the relationship between the ratio of soluble hemoglobin scavenger receptor 163 protein(sCD163)/soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)in plasma and prognosis in patients with spontaneous acute cerebral hemorrhage(ACH).Methods From August 2020 to August 2022,90 patients with ACH admitted to the Department of Neurosurgery,Harison International Peace Hospital,Hengshui City were regarded as the research group.According to the Glasgow outcome scale,patients with ACH were separated into the poor prognosis group(n=38)and the good prognosis group(n=52).Another 45 healthy examinee who underwent physical examination were used as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect plasma sCD163 and sTWEAK levels,and the sCD163/sTWEAK ratio was calculated.Pearson method was applied to analyze the correlation between plasma sCD163,sTWEAK levels,sCD163/sTWEAK ratio and clinical data.Logistic regression was applied to analyze influencing factors of poor prognosis in patients with ACH.Receiver operating characteristic(ROC)was applied to analyze the predictive value of sCD163/sTWEAK ratio for poor prognosis of patients with ACH.Results The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously higher in the research group than those in the control group(P＜0.05).The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously lower in the good prognosis group than those in the poor prognosis group(P＜0.05).Hematoma volume,National Institutes of Health Stroke Scale(NIHSS)scores,hypertension and subtentorial hemorrhage were lower in the good prognosis group than those in the poor prognosis group,and low density lipoprotein cholesterol(LDL-C)was higher in the good prognosis group than that in the poor prognosis group(P＜0.05).Correlation analysis showed that plasma sCD163,and sTWEAK levels and the sCD163/sTWEAK ratio were positively correlated with bleeding site,hematoma volume,NIHSS score,white blood cell count,platelet count and neutrophil/lymphocyte ratio(NLR)(P＜0.05).Results of Logistic regression analysis showed that sCD163,sTWEAK,sCD163/sTWEAK ratio,hematoma volume,bleeding site and NIHSS score were influencing factors for poor prognosis in patients with ACH(P＜0.05).Results of receiver operating characteristic showed that the AUC of sCD163/sTWEAK ratio in evaluating poor prognosis of patients with ACH was 0.850,and the sensitivity and specificity were 86.84%and 69.23%.Conclusion The sCD163/sTWEAK ratio has a high level in the plasma of patients with ACH,which is associated with poor prognosis and has important value in predicting the prognosis of patients with ACH.

Post traumatic depression (PTD) is a serious complication after traumatic brain injury, with high incidence rate; PTD seriously affects the rehabilitation, outcome and quality of life of patients. Due to unclear pathogenesis of PTD, effective treatments have not yet been found in clinical practice. Repetitive transcranial magnetic stimulation (rTMS), as a new non-invasive neuroregulatory technique, has been used in major depression disorder (MDD). Few clinical evidence on PTD treated by rTMS is noted and optimal rTMS treatment regimen has not yet been defined.This article reviews the clinical studies of rTMS in PTD in recent years, with a view to provide references for clinical application.

Pigeons show flocking and homing behaviors,which require characteristics including long-distance weight-bearing and continuous flight,with excellent navigation and spatial cognitive abilities.Pigeons have been widely used in animal robot research in recent years.Pigeon robots achieve motor behavior control by applying neural information intervention to specific neural targets in the pigeon's brain.This review summarizes research progress in pigeon robots based on the sensory system,motivation and emotional system or cortex and midbrain motor area respectively,according to the distribution of hierarchical multi-level neural regulatory targets in the pigeon's brain,with the aim of providing reference and guidance for further applied research into the use of pigeon robots in space perception,reconnaissance,and anti-terrorism search and rescue.

Objective:To analyze the correlation between the skin temperature changes in the radiation area and the occurrence of radiodermatitis during postoperative radiotherapy for female breast cancer and to explore the application value of skin temperature monitoring in the early warning of radiodermatitis risks.Methods:A total of 103 patients who received three-dimensional conformal radiotherapy after radical mastectomy in the Fourth Hospital of Hebei Medical University were continuously enrolled from May to November, 2022 in this study. Their skin temperature in the radiation area and radiodermatitis were recorded weekly. The relationships between relative skin temperature differences and different grades of radiodermatitis were determined. The optimal cut-off values for grade ≥ radiodermatitis were calculated, and the predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Furthermore, the radiodermatitis risks under different skin temperatures were compared using binary logistic regression.Results:There was a positive correlation between the skin temperature in the radiation field and the grade of radiodermatitis. The optimal cut-off values for the average relative skin temperature difference of the chest wall (under 40 Gy/20 fractions), the maximum relative skin temperature difference of the chest wall (under 40 Gy/20 fractions), and the relative skin temperature difference of the supraclavicular block (under 30 Gy/15 fractions) were 0.45℃, 0.55℃, 0.15℃, respectively. The patients were divided into low- and high-risk groups based on the optimal cut-off values (0.45℃, 0.55℃, and 0.15℃). Binary logistic regression result showed that the risks of grade ≥ 2 radiodermatitis in the high-risk group were 5.71, 4.29, and 5.15 times those in the low-risk group, respectively ( OR = 5.71, 95% CI 1.81-17.99, P = 0.003; OR = 4.29, 95% CI 1.65-11.12, P = 0.003; OR = 5.15, 95% CI 2.16-12.31, P < 0.001). Conclusions:Skin temperature monitoring using medical infrared thermometers can be used to effectively predict the occurrence of grade ≥ 2 radiodermatitis. The skin temperature changes in the radiotherapy area should be closely observed. The risk of grade ≥ 2 radiodermatitis will increase when the mean and maximum relative temperature differences of the chest wall increase by 0.45℃ and 0.55℃, respectively under 40 Gy/20 fractions of radiotherapy or when the relative temperature differences of the supraclavicular block increases by 0.15℃ under 30 Gy/15 fractions of radiotherapy.

Objective:To explore the effects of Undaria pinnatifida polysaccharides(UPPs)on depressive-like behavior,neurotransmitter content,oxidative stress,and the hypothalamus-pituitary-adrenal(HPA)axis in rats treated with chronic unpredictable mild stress(CUMS).Methods:A rat model of depression was prepared using the CUMS method,and rats were treated with normal saline(NS)or different doses of UPPs by gavage.The general condition of the rats was observed,and depressive-like behavior was detected by the open field test(OFT),sucrose preference test(SPT),and forced swimming test(FST).The activity or levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE),malondialdehyde(MDA),superoxide disidase(SOD)and catalase(CAT),adrenocorticotrop-ic hormore(ACTH),corticosterone(CORT)in the hippocampus or serum of rats were detected using commercial kits.Western Blot was used to detect the expression level of hippocampal glucocorticoid receptor(GR)protein,and hema-toxylin-eosin(HE)staining was used to observe the tissue structure of hippocampus of rats.Results:The depressive-like behavior of rats in the UPPs medium and high dose groups was significantly improved(P＜0.05).In the UPPs high dose group,the contents of 5-HT,DA,and NE in the hippocampus of rats increased(P＜0.05),while the con-tents of MDA in both serum and hippocampus decreased(P＜0.05),and the activities of SOD and CAT increased(P＜0.05).The contents of ACTH and CORT in serum decreased(P＜0.05).In the UPPs medium dose group,the levels of hippocampal MDA and CAT,as well as serum SOD,ACTH,and CORT were improved(P＜0.05).The expression level of GR protein in the hippocampus increased(P＜0.05),and the pathological changes in the hipp-ocampal dentate gyrus were significantly improved.Conclusion:UPPs can alleviate depressive-like behavior in CUMS rats,and its mechanism may be related to increasing the content of monoamine neurotransmitters in the hippocampus,reducing oxidative stress damage,and HPA axis hyperfunction.

Objective To analyze the effect of neurofeedback training based on early start Denver model(ESDM)on children with autism spectrum disorder(ASD). Methods From August,2020 to May,2024,a total of 60 children with ASD from Hangzhou Children's Hospital were randomly divided into control group(n=30)and observation group(n=30).The control group received ESDM intervention,while the observation group received neurofeedback training in addition,for six months.They were assessed with Autism Treatment Evaluation Checklist(ATEC)and Psycho-Educational Profile-3rd Edition(PEP-3). Results After treatment,the score of ATEC was lower in the observation group than in the control group(t=3.545,P<0.05),the scores of cognition(t=2.236,P=0.029),emotional expression(t=2.293,P=0.025)and problem be-havior(Z=2.099,P=0.036)were higher in the observation group than in the control group.The score differenc-es of ATEC(Z=3.620,P<0.001),and cognition(Z=2.920,P<0.05)and problem behaviors(Z=4.209,P<0.05)of PEP-3 before and after intervention were higher in the observation group than in the control group. Conclusion Combination of neurofeedback training could improve the effect of ESDM on ASD.

Objective:To explore the clinical and genetic characteristics of three children with Leguis syndrome.Methods:Three children suspected as Legius syndrome at the Henan Children′s Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c. 751C>T (p.Arg251Ter194) in child 1, c. 229A>T (p.Lys77Ter368) in child 2, and c. 1044_1046delinsC (p.R349fs *11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. Conclusion:All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.