Objective:To evaluate the role of aquaporin 4 (AQP4) in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice and the relationship with protein kinase C (PKC).Methods:One hundred and fifty clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), mechanical ventilation group (group V), LY317615 group (group L), dexmedetomidine group (group D), and dexmedetomidine+ PMA group (group DP). Group C spontaneously breathed air for 6 h. The animals were mechanically ventilated for 6 h in group V. PKC inhibitor LY3176 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in group L. Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in D and DP groups. PKC activator PMA 15 μg/kg was intraperitoneally injected at 60 min before mechanical ventilation in group DP. Mice were anesthetized at 1 day after mechanical ventilation, then sacrificed and hippocampal tissues were taken for microscopic examination of pathological changes in the hippocampal CA1 and CA3 areas (with a light microscope). Brain tissues were also taken to measure the water content and content of Evans blue (EB) and to detect the expression of PKC and AQP4 (by Western blot). The cognitive function was evaluated using a novel object recognition task at 3 days after mechanical ventilation. Results:Compared with group C, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group V and group DP. Compared with group V, the water content and EB content of brain tissues were significantly decreased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was down-regulated, the percentage of novel object exploration and discrimination index were increased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was significantly attenuated in group D and group L. Compared with group D, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group DP. Conclusions:AQP4 is involved in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice, and the mechanism is related to inhibiting activation of PKC.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:This study aimed to evaluate the immunoprotective effect of anti-rabies virus cocktail monoclonal antibody Zamerovimab/Mazorelvimab after rabies exposure.Methods:The dynamic data of rabies virus neutralizing antibody (RVNA) were analyzed in the Zamerovimab/Mazorelvimab Chinese phase Ⅲ study (clinical trial registration number: CTR20201819).Results:The full analysis set showed that RVNA geometric mean titers (GMT) on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 4.413 IU/ml, 5.178 IU/ml, 17.062 IU/ml, 14.672 IU/ml, and 2.836 IU/ml, respectively, while those in the human rabies immunoglobulin (HRIG) group were 0.299 IU/ml, 0.451 IU/ml, 11.374 IU/ml, 18.063 IU/ml, and 6.769 IU/ml, respectively. The positive rates of RVNA on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 99.9%, 99.6%, 100%, 100%, and 97.4%, respectively, while those in the HRIG group were 23.3%, 34.1%, 97.6%, 99.6%, and 98.4%, respectively. Conclusions:Compared with HRIG, Zamerovimab/Mazorelvimab cocktail monoclonal antibody reached the required protection level of RVNA very soon, thus effectively provided an immediate neutralizing effect of passive immunization therapies against rabies virus.

Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.

Objective To evaluate the impact of flash glucose monitoring(FGM)system on glycemic control and adverse pregnancy outcome in pregnant women with type 2 diabetes mellitus(T2DM).Methods This prospective,open-label,randomized,controlled clinical trial involved 109 women with T2DM at 16～18 weeks of gestation who visited Liaocheng People's hospital and Liaocheng Women and Children Hospital from June 2018 to June 2022.They were randomly assigned to FGM group(54 cases)and control group(55 cases).The FGM group wore FGM at 20,24,28 and 32 weeks of pregnancy respectively.The Con group underwent self-monitoring of blood glucose(SMBG).Both groups adjusted insulin doses based on blood glucose monitoring results.HbA1c was measured at 18 weeks and 36 weeks of pregnancy.Information related to adverse pregnancy outcomes was compared between the two groups.Results Fasting and postprandial glucose and HbA1c were significantly lower in FGM group compared with con group(P<0.05).Neonatal hypoglycemia was significantly lower in FGM group(P<0.05).There was no difference between the two groups in terms of BMI,insulin dose,gestational week of delivery,Apgar score,neonatal weight and the incidence of preeclampsia,premature delivery,polyhydramnios,cesarean section,SGA,macrosomia and postpartum hemorrhage(P>0.05).Time in range(TIR),time below range(TBR),time above range(TAR),and mean amplitude of glucose excursion(MAGE)were significantly improved at 32 weeks compared to 20 weeks in FGM group(P<0.05).Conclusions Repeated intermittent use of FGM in pregnant women with T2DM could reduce the blood glucose level and the incidence of neonatal hypoglycemia.

Diabetes mellitus(DM)stands as a chronic metabolic ailment predominantly characterized by elevated blood glucose lev-els,stemming from either a resistance to insulin or aberrations in insulin secretion.The ensuing persistent hyperglycemia,a direct con-sequence of pancreatic β-cell devastation,acts as a catalyst for a myriad of complications,inclusive of extensive neuropathies.The dis-ease has substantial prevalence and mortality rates,underscoring the gravity of its impact on public health.Dental pulp stem cells(DPSCs)are readily obtainable,and they exhibit a profound capacity for self-renewal,multi-lineage differentiation,and vigorous pro-liferation.Remarkably,DPSCs can differentiate into pancreatic β-cells,subsequently participate in insulin secretion and play a pivotal role in immune modulation.This has achieved notable advancements in the therapeutic domain,particularly in the treatment of chronic diseases.Furthermore,DPSCs harbor the potential to mitigate symptoms in patients afflicted with type 1 diabetes.They navigate this therapeutic pathway through mechanisms that involve suppressing autoimmunity,modulating inflammatory responses,and counteracting oxidative stress.This article meticulously reviews the biological characteristics inherent to DPSCs and explores their multifaceted thera-peutic potential in addressing DM and its associated complications.Through this endeavor,the article aims to contribute to the refine-ment and enhancement of DM management strategies.

Objective To explore the relationship between symptom burden and disease uncertainty in patients with chronic heart failure(CHF),and verify the moderating effect of health literacy on symptom burden and disease uncertainty.Methods A total of 234 patients with CHF who were hospitalized in the First Affiliated Hospital of Wenzhou Medical University from April 2021 to April 2022 were selected by convenience sampling method.Memorial symptom assessment scale-heart failure,Mishel uncertainty in illness scale for adult,and health literacy management scale were used for questionnaire surveys.Multiple linear regression was used to verify the moderating effect of health literacy on symptom burden and disease uncertainty in CHF patients.Results The symptom burden of CHF patients was positively correlated with disease uncertainty(r=0.497,P＜0.01),and negatively correlated with health literacy(r=-0.252,P＜0.01),health literacy was negatively correlated with disease uncertainty(r=-0.593,P＜0.01).Moderating effect analysis showed that health literacy had a moderating effect between symptom burden and disease uncertainty in CHF patients(β=-0.258,P＜0.05).Simple slope analysis showed that when the health literacy level of CHF patients was high,symptom burden had less positive predictive effect on disease uncertainty(simple slope=6.817,P＜0.05).Conclusion The symptom burden of CHF patients can affect the level of disease uncertainty and is regulated by health literacy.Nursing should pay attention to the effect of symptom burden on the level of disease uncertainty in CHF patients,and formulate interventions to reduce the symptom burden and improve health literacy,so as to reduce the level of disease uncertainty.

Objective: To explore the association between exposure to bedroom night light during sleep and emotional symptoms in children and provide a scientific basis for subsequent effective prevention and intervention. Methods: In December 2021, 1 926 students from grades 4 to 6 were recruited to conduct a student questionnaire survey in two primary schools in Tianchang of Chuzhou City, Anhui Province. The data, including general demographic information, use of night lights and curtains, emotional symptoms, and other information, was collected. Binary Logistic regression analysis was used to examine the correlation between night light use and children s emotional symptoms. Results: The reporting rates of depression symptoms, generalized anxiety symptoms, social phobia, and obsessive compulsive symptoms of the children were 2.5%, 2.6%, 3.4% and 2.5%, respectively. About 12.6% of children often sleep with a night light on, and 22.0% of children did not close the curtains. Binary Logistic regression analysis revealed that frequent sleep with night lights was associated with an increased risk of depression symptoms( OR=2.29, 95%CI = 1.04- 5.03), social phobia ( OR=1.93, 95%CI =1.02-3.64) and obsessivecompulsive symptoms ( OR=3.44, 95%CI =1.72-6.88) in children( P < 0.05). Conclusion There is a positive correlation between bedroom night light exposure during sleep and the detection rate of children s emotional symptoms. The attention should be paid to bedroom light environment of children during sleep to reduce the adverse effects of night light exposure on the mental health.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

ObjectiveTo explore the differences between the ancient decocting methods and modern decocting method of Yihuangtang by taking the dry extract rate， the content of active ingredients and the fingerprint information as indicators， so as to provide reference for the preparation of benchmark samples and the development of compound preparations of this famous classical formula. MethodAccording to the three decocting methods recorded in Paozhi Dafa and Jianming Yigou and Management Specifications of Traditional Chinese Medicine Decoction Chambers in Medical Institutions， the Yihuangtang was decocted respectively. The polysaccharide content in the samples was determined by ultraviolet spectrophotometer （UV） at 488 nm， and the contents of alkaloids （berberine hydrochloride， phellodendrine chloride and magnoflorine） in the samples and their fingerprint profiles were determined by high performance liquid chromatography （HPLC）， and the dry extract rate was combined to compare the differences of the three decocting methods of Yihuangtang. Among them， the fingerprint was gradient eluted with acetonitrile （A） -0.1% phosphoric acid aqueous solution （B） as mobile phase （0-10 min， 5%-8%A； 10-35 min， 8%A； 35-45 min， 8%-12% A； 45-75 min， 12%-17%A； 75-105 min， 17%-35%A； 105-110 min， 35%-100%A； 110-112 min， 100%-5%A； 112-122 min， 5%A）， and the detection wavelength was 230 nm. ResultWhen the decoction was carried out according to the method described in Paozhi Dafa， the content of polysaccharides was higher than that of the modern decocting method and the method described in Jianming Yigou. However， the contents of berberine hydrochloride， phellodendrine chloride and magnoflorine were the highest in the modern decocting method. Meanwhile， the number of peaks in fingerprint of the samples prepared by the three decocting methods was basically the same， and 13 common peaks were matched， and the three common peaks of berberine hydrochloride， phellodendrine chloride and magnoflorine were identified. However， the relative peak areas of the common peaks in the fingerprint of the samples prepared by the three decocting methods varied greatly， suggesting that there were differences in the extracting effects of different decocting methods. In addition， there were also differences in the dry extract rate among the three decocting methods of Yihuangtang， and the highest value was obtained by decocting the samples according to the method recorded in Paozhi Dafa. ConclusionDecocting method can affect the dry extract rate， fingerprint information and active ingredient content of Yihuangtang， among which the modern decocting method is conducive to the extraction of alkaloids and the preparation transformation of this famous classical formula， and it is recommended to determine its preparation process by optimizing the modern decocting method.