ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment （温阳生肌膏， WSO） in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the Beifuxin （Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the Beifuxin group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue. ResultsCompared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （P＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （P＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and Beifuxin group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （P＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （P＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the Beifuxin group （P＜0.05 or P＜0.01）. Compared with the Beifuxin group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （P＜0.05）. ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet. Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice. Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m⁻³ PHMG), and high-dose (1.0 mg·m⁻³ PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry. Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count [(1.49±0.22)×10⁹·L⁻¹], lymphocyte count [(0.96±0.36)×10⁹·L⁻¹] and its proportion [(63.13±14.96)%] in the peripheral blood of mice in the high-dose group were lower than those in the control group [(2.69±0.25)×10⁹·L⁻¹, (2.33±0.28)×10⁹·L⁻¹, and (86.23±3.40)%, respectively] (P<0.01), whereas red blood cell count [(12.32±0.46)×10¹²·L⁻¹], hemoglobin count [(175.25±4.65) g·L⁻¹], and hematocrit [(53.55±0.70)%] in the peripheral blood of mice in the high-dose group were higher than those in the control group [(11.11±0.37)×10¹²·L⁻¹, (160.67±4.04) g·L⁻¹, and (45.10±9.75)%, respectively] (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05). Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.

Objective:To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies.Methods:A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results:Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions:Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Objective: To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. Methods: This multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. Conclusion The results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Objective To investigate the effect and potential mechanism of early exercise intervention on cerebral myelin in cerebral ischemia rats.Methods A total of 18 SD rats were randomly divided into the sham group,the middle cerebral artery occlusion resting group(MCAO-SED)and the middle cerebral artery occlusion exercise group(MCAO-EX),with 6 rats in each group.Except the sham group,the middle cerebral artery occlusion model was prepared by modified Longa line embolization method in other groups.After modeling,rats in the MCAO-EX group were placed on a treadmill for exercise intervention for 28 days.Neurological function was assessed by modified neural function deficit score(mNSS).Infarct volume was detected by MRI scanning(T2),myelin basic protein(MBP)expression was detected by immunofluorescence.Myelin sheath structure was detected by transmission electron microscopy.Western blot assay was used to detect endoplasmic reticulum stress-related protein expression.Apoptosis was detected by TUNEL staining.Results After 28 days of intervention,compared with the MCAO-SED group,the nerve function recovered well in the MCAO-EX group,infarct volume decreased,myelin integrity increased,MBP fluorescence intensity expression increased and MBP expression level increased.The expression levels of ATF6,p-IRE1,p-PERK and cleaved caspase 3 were significantly decreased,and apoptosis was reduced.Conclusion Early exercise can inhibit endoplasmic reticulum stress-induced apoptosis,promote cerebral myelin repair,reduce infarct size and improve nerve function.

AIM:To investigate the effects of the compound ANBP on wound healing in diabetic rats and ex-plore its mechanism of action.METHODS:Ninety male SD rats were randomly divided into blank,model,compound ANBP,Beifuxin,and nicotinamide mononucleotide(NMN)groups,with 16 rats in each group.Wound healing in each group was observed and samples were taken on days 3,7 and 14 to analyze the wound healing rate.Local histopathological changes were observed using HE and Masson staining.The expressions of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),citrate synthase(CS),isocitrate dehydrogenase(IDH1)and oxoglutarate dehydrogenase(OGDH)were de-tected through immunofluorescence and Western blot.The number and morphology of mitochondria in the wound tissue were observed using transmission electron microscopy.RESULTS:Histomorphological changes revealed significant im-provement in diabetic wound healing in the blank and compound ANBP groups compared to that of the model group.The wound healing rates of the blank,compound ANBP,Beifuxin,and NMN groups were significantly increased on days 3,7,and 14(P<0.01).Compared to the model group,granulation tissue generation was higher in the other groups,cover-ing the wound defect and producing abundant collagen fibers.At 3,7,and 14 days after intervention,the blank,com-pound ANBP,Beifuxin,and NMN groups showed significantly enhanced fluorescence intensities of TCA cycling-related enzymes PDHA1,CS,IDH1,and OGDH indicating increased expression of these enzymes.The levels of the TCA cy-cling-related enzymes were significantly increased(P<0.01)in the compound ANBP,Beifuxin and NMN groups but were significantly decreased(P<0.01)in the model group.An increase in the number and density of mitochondria and a de-crease in the cavitation rate of mitochondria with improved morphology(P<0.05)was observed in the group treated with compound ANBP.CONCLUSION:Compound ANBP may increase the number of mitochondria,improve mitochondrial morphology and function,upregulate the expression levels of PDHA1,CS,IDH1,and OGDH proteins,and accelerate the regeneration of wound granulation tissue,thus promoting the healing of diabetic wounds in rats.

Objective:To summarize emergency rescue capacity evaluation tools for community nurses.Methods:China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, PubMed, Embase, CINAHL, Web of Science core collection, and other databases were searched by computer, and the search period was from the establishment of the databases to April 23, 2023. The relevant contents of emergency rescue capacity evaluation tools for community nurses were extracted and analyzed.Results:A total of 16 articles were included, involving seven kinds of emergency rescue capacity assessment tools for community nurses. The evaluation methods of the tools were all self-evaluation. The evaluation mainly involved the ability of nurses in four stages of emergency rescue prevention, preparation, response, and recovery.Conclusions:There are limitations in the evaluation content, method, and application effect of the emergency rescue capacity evaluation tools for community nurses. In the future, it is still necessary to develop or introduce foreign emergency rescue capacity evaluation tools with comprehensive evaluation content and good reliability and validity.

Vitamin D(VD)is a fat-soluble vitamin closely related to bone health and calcium and phosphorus metabolism.VD deficiency in humans has become a global public health problem,especially in pregnant women as it affects maternal health and fetal growth,develo-pment,and susceptibility to many diseases.Recent studies have shown that adequate cord blood VD levels are associated with a reduced incidence of eczema in infants aged<1 year.With the increasing annual incidence of eczema in infants,its association with VD nutritional status has begun to receive attention.However,few epidemiological studies have investigated the association between VD levels during pregnancy and infantile eczema,and the results have been inconsistent.Therefore,this study reviews the association between VD nutri-tional status during pregnancy and infantile eczema,which may provide a theoretical basis for further exploring the role of VD nutritional status in the development of infantile eczema and taking targeted preventive and curative measures.

Objective　To investigate the relationship between exosomal microRNA (miR)-335-5p and the severity of cirrhosis in patients with chronic hepatitis B (CHB), in order to provide more clinical information for early intervention and treatment. Methods From February to August 2019, 6 healthy controls, 8 cases of compensated cirrhosis (CLC), and 8 cases of decompensated cirrhosis (DLC) were recruited from the physical examination outpatient department and the hepatology department of Peking University Third Hospital Qinhuangdao Hospital as a discovery cohort, and serum samples were collected for exosome extraction and miRNA microarray analysis. A validation cohort of 229 CHB patients with cirrhosis, including 94 CLC and 135 DLC patients, was selected from those diagnosed and treated in the hepatology department of the hospital from December 2019 to May 2022. Exosomes were extracted and identified, and the expression level of serum exosomal miR-335-5p was detected by real-time fluorescence quantitative PCR. The model for end-stage liver disease (MELD) score and the combined formula of serum sodium with MELD (MELD-Na) score were used to evaluate the severity of cirrhosis. Results In the discovery cohort, the expression of miR-335-5p in the DLC group was significantly down-regulated compared to the control group and CLC group (P<0.05). In the validation cohort, the level of exosomal miR-335-5p in the DLC group was significantly lower than that in the CLC group (P<0.001). Spearman correlation analysis showed a negative correlation between the expression of exosomal miR-335-5p and both MELD and MELD-Na scores in patients with cirrhosis (P<0.05). After adjusting for other confounding factors in the multiple linear regression model, the expression of exosomal miR-335-5p was still negatively correlated with MELD score (β=-0.103, 95%CI:-3.692 to -1.149, P<0.001) and MELD-NA score (β=-0.109, 95%CI:-4.007 to -1.270, P<0.001). ROC curve analysis indicated that serum exosomal miR-335-5p could differentiate DLC with an area under the ROC curve of 0.905 (95%CI: 0.867 to 0.944), corresponding to a cutoff value of 0.158, with a specificity of 87.2%, and a sensitivity of 83.7%. Conclusions The low expression of exosomal miR-335-5p is associated with the aggravation of cirrhosis in CHB patients, and may serve as a useful biomarker for the early diagnosis of DLC.