Objective To observe the effects of AnMeiDan(AMD),a representative formula of Peiyuan Guben Tranquilisation method,on the learning memory of zebrafish model of sleep deprivation(SD),and to explore the possible mechanism and the optimal apparent dose based on the Orexin signalling pathway.Methods 120 4-month-old wild-type AB line zebrafish were randomly divided into blank group,model group,AMD low-dose group(0.009 mg·mL-1·d-1),AMD medium-dose group(0.027 mg·mL-1·d-1),AMD high-dose group(0.081 mg·mL-1·d-1),and melatonin group(0.4 mg·mL-1·d-1).Zebrafish SD model was established by LED light induction method,24 h behavioural changes of zebrafish in each group were monitored by zebrafish behavioural tracking system,differences in learning and memory ability of zebrafish in each group were detected by T-maze,the state and number of neurons in the brain of zebrafish in each group were observed by Hematoxylin-Eosin(HE)staining method,the structural changes of neurons in the brain of zebrafish in each group were observed by transmission electron microscopy,and changes in neuron structure in the brain of zebrafish in each group were detected by ELISA method.The levels of Orexin A(OXA)and Orexin B(OXB)in zebrafish were detected by enzyme-linked immunosorbent assay(ELISA),and the protein and mRNA expression levels of OXA/p38 mitogen-activated protein kinase(P38 MAPK)/extracellular regulated protein kinase(ERK1/2)were detected by protein immunoblotting and real-time fluorescence quantitative assay(RT-PCR)in zebrafish.Results Compared with the blank group,the total number of rests,duration and distance were reduced in the model group(P<0.05),and the latency to enter the target region(OR)was prolonged(P<0.01);the number of neuronal cells was reduced,the nuclei were degenerated(P<0.01),cytoplasmic hyalinosis was increased(P<0.01),and light colouring was observed,the nuclei were collapsed,the nuclear membranes were ruptured and lysed,the chromatin was solidified,and the mitochondria were swollen and deformed with internal cavities,and lamellipod-like myelin-like structure was formed;the brain tissue OXA,OXA,and ERK1/2 expression levels of the mRNAs and the mRNAs of these signaling pathways were increased(P<0.01).brain tissue OXA and OXB proteins were significantly elevated,OXA mRNA and protein were significantly up-regulated,and P38 MAPK and ERK1/2 mRNA and protein were significantly down-regulated(P<0.01).Compared with the model group,the drug intervention could prolong the total resting exercise time of SD zebrafish(P<0.05);shorten the latency of zebrafish to reach OR(P<0.05);protect the structure and morphology of neuronal cells,and alleviate the damage of brain tissues;reduce the content of OXA and OXB in the brain tissues(P<0.01);and down-regulate the expression of OXA mRNA and protein(P<0.01),and up-regulate the P38 MAPK and ERK1/2 mRNA and protein expression of P38 MAPK and ERK1/2(P<0.01);and the quantity-effect relationship was obvious,and the effect of high dose of AMD was optimal.Conclusion AMD can improve the learning and memory ability in zebrafish SD model,and its mechanism may be related to the regulation of OXA/P38 MAPK/ERK1/2 signalling pathway and alleviation of neuronal damage in the brain,and the high dose group of AMD showed the best effect.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

OBJECTIVE To study the chemical composition and analgesia molecular mechanism of Shuanghu Zhongtongning tincture by UPLC-Q-TOF-MS/MS and network pharmacology. METHODS By comparing the chromatogram and blank chromatogram of Shuanghu Zhongtongning tincture, combined with PubChem, HMDB, MassBank database spectrum and the lysis information of reference substance, the chemical composition of Shuanghu Zhongtongning tincture was analyzed and identified. Protein-protein interaction network was constructed by using STRING database, and potential targets of analgesic effect of Shuanghu Zhongtongning tincture were screened. And GO and KEGG enrichment analysis were performed to analyze the core pathways related to analgesia. The network of "chemical composition-disease-target" was constructed by Cytoscape software to analyze the key compounds related to analgesia. RESULTS Seventeen core components of neochlorogenic acid, chlorogenic acid, hesperidin, neohesperidin, ferulic acid, berberine, ursolic acid, deoxyaconitine, mesaconitine, hypaconitine, benzoylmesaconine, benzoylhypacoitine, caffeic acid, quercetin, oleanolic acid, 4-hydroxycinnamic acid and mefenamic acid were identified, 3 core targets of STAT3, MAPK3 and MAPK1 were found, and 4 key signaling pathways of IL-17, TNF, PI3K-Akt and arachidonic metabolism were revealed. CONCLUSION This study preliminarily clarifies the chemical composition of Shuanghu Zhongtongning tincture and potential mechanism of analgesic effect, and provides a scientific theoretical basis for the study on the material basis and mechanism of Shuanghu Zhongtongning tincture.

Background: and Purpose Collateral circulation is considered an important factor affecting the risk of stroke, but the factors that affect collateral circulation remain unclear. This study was performed to identify the factors associated with collateral circulation, especially blood lipids. Methods: The study involved patients who had undergone digital subtraction angiography and were confirmed as having severe unilateral stenosis or occlusion of the internal carotid artery (ICA). We classified the collateral circulation status of each patient as good (Grade 3 or 4) or poor (Grade 0, 1, or 2) according to the grading system of the American Society of Interventional and Therapeutic Neuroradiology/American Society of Interventional Radiology. We collected data on patients’ characteristics and identified the factors that affect collateral circulation. Results: This study included 212 patients. The multivariate logistic regression analysis showed that the high-density lipoprotein cholesterol (HDL-C) concentration and a complete anterior half of the circle of Willis were independent protective factors for good collateral circulation, whereas elevated lipoprotein(a) [Lp(a)] and serum creatinine concentrations were independent risk factors for good collateral circulation. The area under the receiver operating characteristics curve (AUC) was 0.68 (95% confidence interval [CI], 0.61–0.76) for HDL-C and 0.69 (95% CI, 0.62–0.76) for Lp(a). A binary logistic regression model analysis of the joint factor of HDL-C and Lp(a) yielded an AUC of 0.77 (95% CI, 0.71–0.84). Conclusions In patients with severe unilateral ICA stenosis or occlusion, the combination of HDL-C and Lp(a) is a useful predictor of collateral circulation.

Objective:To investigate the nutritional and metabolic risk factors associated with recurrence in patients with newly diagnosed ulcerative colitis (UC), so as to allow better clinical prediction of recurrence.Methods:A retrospective cohort study was conducted. Patients newly diagnosed with UC (mild and moderate) from the People's Hospital of Xinjiang Uygur Autonomous Region were screened based on prespecified inclusion and exclusion criteria from January 2016 to January 2019. Patients were followed up regularly for three years. Subgroups were determined according to the presence or absence of recurrence. The patients in the UC recurrence group were further stratified according to the time to recurrence into short-term (0-6 months), mid-term (6-12 months) and long-term (12-36 months) recurrence groups. The nutritional and metabolic risk factors related to recurrence were evaluated by univariate analysis and multifactorial logistic regression analysis, and the predictive value was evaluated via receiver operating characteristic curve. The risk factors were then compared across the 3 subgroups with recurrence.Results:A total of 210 patients newly diagnosed with UC (mild and moderate) were included, including 38 experiencing recurrence within 0-6 months, 27 within 6-12 months, 24 within 12-36 months, and 121 without recurrence. There were no statistically significant differences in gender, age, smoking history, and family history in the recurrence group compared with the non-recurrence group. Univariate analysis suggested significant differences in homocysteine, folate, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A/B (ApoA/B), 25-hydroxy vitamin D 3, and body mass index (BMI) between recurrence and non-recurrence groups ( P < 0.05). Multifactorial binary logistic regression analysis suggested that homocysteine ( OR = 0.869, 95% CI: 0.782 to 0.965, P = 0.009), triglycerides ( OR = 0.176, 95% CI: 0.060 to 0.519, P = 0.002), LDL ( OR = 0.256, 95% CI: 0.089 to 0.733, P = 0.011), 25-hydroxy vitamin D 3 ( OR = 0.937, 95% CI: 0.895 to 0.0.982, P = 0.006), and BMI ( OR = 1.319, 95% CI: 1.162 to 1.498, P < 0.01) were independent risk factors for UC recurrence. The predictive efficiency of individual risk factors in descending order was as following: LDL (AUC = 0.762, Youden's index [YI] = 0.42, cut-off value = 2.345), triglycerides (AUC = 0.718, YI = 0.361, cut-off value = 1), homocysteine (AUC = 0.666, YI = 0.283, cut-off value = 13.265). There were no statistically significant differences in gender, age, smoking history, and family history across the short-term, mid-term and long-term recurrence groups. There were significant differences in HDL and ApoA/B levels between the short-term and the long-term recurrence groups ( P < 0.05). Conclusions:Recurrence of the disease in UC patients results from the combined effects of multiple factors. The changes in homocysteine, triglycerides, LDL, 25-hydroxy vitamin D 3, and BMI in UC patients should be proactively monitored to prevent recurrence.

Objective:To explore the influencing factors of drug application deviation in elderly diabetes mellitus patients during hospital-family transition period.Methods:A total of 278 elderly diabetes mellitus patients in Henan Provincial People's Hospital from March 2019 to March 2021 were selected as the study subjects.All patients were followed up by telephone 1 week after discharge.The drug deviation evaluation tool(MDT)was used to evaluate the drug application deviation in patients during the hospital-family transition period.They were divided into drug application deviation group and non-drug application deviation group.Sociodemographic and disease-related data and medication management data were compared between the two groups.Logistic regression analysis was used to analyze the influencing factors of drug application deviation in elderly patients with diabetes mellitus during hospital-family transition period.Results:Of the 278 elderly patients with diabetes, 162(58.27%)had at least one drug application deviation during hospital-family transition period.The family care index was lower in drug application deviation group than non-drug application deviation group( Z=6.578, P<0.001).As compared with non-drug application deviation group, drug application deviation group had the higher number of drugs at discharge, and had lower scores of Morisky Medication Adherence Scale with Eight-Item(MMAS-8), had lower scores of Summary of Diabetes Self Care Activities(SDSCA)and had lower scores of Self-efficacy for Appropriate Medication Use Scale(SEAMS), with statistically significant differences( Z=10.971, 6.077, t=5.947, 14.105, all P<0.001).Binary Logistic regression analysis and forest map showed that the more number of discharge medication was a risk factor for drug application deviation during hospital-family transition period in elderly patients with diabetes mellitus( OR=4.128, P<0.001); family care index, MMAS-8 score, SDSCA score and SEAMS score were its protective factors( OR=0.343, 0.523, 0.922, 0.568, all P<0.05). Conclusions:The incidence of drug application deviation during hospital-family transition period is higher in elderly patients with diabetes mellitus.The possible protective factors are high scores of family care index, MMAS-8, SDSCA and SEAMS, and the risk factor is large number of drugs ordered by discharged doctors.Therefore, targeted intervention measures can be implemented to reduce the occurrence of drug application deviation during hospital-family transition period.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Objective:To investigate the impact of a reduced portacaval shunt on hepatic myelopathy (HM) in patients with cirrhosis after a transjugular intrahepatic portosystemic shunt (TIPS).Methods:Patients who developed HM after receiving TIPS at the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to June 2018 were retrospectively analyzed. HM severity was quantified by clinical spasticity index (CSI) and Fugl-Meyer Assessment (FMA) of the lower extremity. Clinical manifestations were combined with grades Ⅰ-Ⅳ. HM patients were divided into drug treatment (group A) and flow restriction group (group B) according to different treatment methods. The changes in CSI and FMA of the lower extremity after treatment were statistically analyzed in the two groups. P<0.05 was considered a statistically significant difference. Results:A total of 421 cases of cirrhosis who underwent TIPS were enrolled. Among them, 30 developed HM, with 22 in group A and 8 in group B. The incidence of HM after TIPS surgery was about 7.13%. After treatment, CSI was gradually increased and FMA of lower extremity was gradually decreased in group A, while vice-versa in group B. CSI in the two groups were differed significantly at 6, 12, 18, and 24 months after treatment ( P<0.05), while the difference in FMA of the lower extremity was statistically significant at 12, 18, and 24 months after treatment ( P<0.05). CSI was decreased and FMA of lower extremity was increased after treatment in patients with group A HM grade I. CSI, and FMA of lower extremity changes were statistically significant ( P<0.05) when compared with patients with HM grades Ⅱ-Ⅳ. The incidence of hepatic encephalopathy was significantly lower in group B than that in group A ( P=0.034), but there was no statistically significant difference between the two groups in the incidence of gastrointestinal bleeding, ascites, infection, MELD score and mortality. Conclusion:A reduced portacaval shunt can improve HM in patients with liver cirrhosis after TIPS, and drug therapy alone is effective for patients with early HM grade I.

Objective: To discuss the correlation between growth status and eating behaviors in children with attention deficit and hyperactivity disorder (ADHD), providing reference data for management and dietary behavior guidance among ADHD children. Methods: A total of 703 children aged 4-13 years old were collected from the ADHD patients from Children s Health Department of Children s Hospital of Nanjing Medical University from June to September, 2019. The demographic characteristics and information regarding children’s eating behaviors were collected by self-designed questionnaire and Chinese version of the parent-completed Children’s Eating Behavior Questionnaire(CEBQ). The correlation physical growth with dietary behaviors among the ADHD children were analyzed. Results: Food avoidant behaviors, including satiety responsiveness, slowness in eating and emotional undereating in ADHD children with thinness scored significantly higher than that of children with short stature, overweight and obesity(F=17.57, 29.32, 4.07, P<0.01), while food approach behaviors, including food responsiveness, enjoyment of food, desire to drink and emotional overeating scored higher in obese children, compared to other three groups(F=24.54, 47.44, 2.96,5.85, P<0.05). Multiple linear regression analysis showed that, after adjusting for the confounders, satiety responsiveness, slowness in eating were still negatively associated with BMI-Z score of the ADHD children(B=-0.05, -0.07, P<0.01). Food responsiveness, enjoyment of food and emotional overeating had a positive association with the BMI-Z score(B=0.04, 0.09, 0.05, P<0.05). Conclusion Emotional eating and high food responsiveness in ADHD children are associated with the overweight and obesity, while long eating time and high satiety responsiveness is associated with underweight among ADHD children. For clinical doctors and parents, problematic eating behaviors among ADHD children should be concerned regarding its negative effects on growth and development, besides core symptoms of ADHD.

Sleep is a complex physiological process of great significance to physical and mental health, and its research scope involves multiple disciplines. At present, the quantitative analysis of sleep mainly relies on the "gold standard" of polysomnography (PSG). However, PSG has great interference to the human body and cannot reflect the hemodynamic status of the brain. Functional near infrared spectroscopy (fNIRS) is used in sleep research, which can not only meet the demand of low interference to human body, but also reflect the hemodynamics of brain. Therefore, this paper has collected and sorted out the related literatures about fNIRS used in sleep research, concluding sleep staging research, clinical sleep monitoring research, fatigue detection research, etc. This paper provides a theoretical reference for scholars who will use fNIRS for fatigue and sleep related research in the future. Moreover, this article concludes the limitation of existing studies and points out the possible development direction of fNIRS for sleep research, in the hope of providing reference for the study of sleep and cerebral hemodynamics.
Brain/diagnostic imaging* ; Hemodynamics ; Humans ; Polysomnography ; Sleep ; Spectroscopy, Near-Infrared