BACKGROUND:Previous studies have shown that puerarin can inhibit the differentiation of osteoclasts,and the expression of Notch signaling pathway-related proteins such as Notch1,HES1,and Jagged1 is decreased.However,the specific mechanism of the Notch1 signaling pathway for the inhibition of osteoclast differentiation by puerarin is not clear. OBJECTIVE:To explore the effect of Notch signaling pathway on puerarin inhibiting the differentiation of mouse macrophage Raw264.7 into osteoclasts. METHODS:Raw264.7 cells were divided into seven groups for intervention culture.Blank control group was cultured in high-sugar DMEM medium;the osteoclast induction group was cultured in osteoclast induction medium;the puerarin intervention group was cultured with 50 μmol/L puerarin at the same time of osteoclast induction;Notch1 siRNA control group,Notch1 siRNA group,Notch1 overexpression control group and Notch1 overexpression group were transfected with Notch1 siRNA control sequence,Notch1 siRNA,Notch1 overexpression control plasmid and Notch1 overexpression plasmid,respectively,and then cultured with osteoclast induction medium and puerarin.The number and size of osteoclasts were observed by tartrate-resistant acid phosphatase staining,the skeleton formation of osteoclasts was observed by F-actin staining,and the gene expression level of osteoclast formation markers was detected by RT-PCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining results showed that puerarin intervention could inhibit the generation of osteoclasts,Notch1 silencing could further reduce the number of osteoclasts,while the number of osteoclasts in the osteoclast-induced group increased significantly after Notch1 overexpression.The results of F-actin showed that Raw264.7 cells could form a well-defined F-actin ring after osteoclast induction.Puerarin intervention would inhibit the formation of cytoskeleton,and Notch1 silencing could aggravate the inhibitory effect of cytoskeleton formation,while Notch1 overexpression could alleviate this inhibitory effect of puerarin.RT-PCR results showed that puerarin could inhibit the mRNA expression levels of tartrate-resistant acid phosphatase,Cathepsin K and c-Fos,the expression of the above-mentioned three factors decreased significantly after Notch1 gene silencing,and Notch1 overexpression could upregulate the expression of these factors.These finding indicate that puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway.

Objective To explore the application effect of enteral nutrition-related diarrhea in postoperative esophageal cancer patients.Methods Based on literature search and expert meeting,a management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients was constructed.A convenience sampling method was used to select a total of 68 patients with enteral nutrition-related diarrhea after esophageal cancer surgery admitted to the thoracic surgery department of a tertiary A cancer hospital in Jiangsu Province.Among them,patients admitted from January 2022 to December 2022 were set as an experimental group.The experimental group was implemented the management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients.Those admitted from January 2021 to December 2021 were set as a control group with routine nursing.Then,the time of stopping diarrhea,the King's of Stool Chart(KSC-Tr)diarrhea score,and abnormal incidence of nutrition-related indexes,electrolytes abnormalities(low sodium,low potassium,and low calcium)were compared between 2 groups.Results The time of stopping diarrhea,KSC diarrhea score after 3 days of intervention and the time to achieve target feeding volume of the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.05).There were no significant differences in hemoglobin,albumin,prealbumin after 3 days of intervention,the incidence of electrolyte abnormalities(low sodium,low potassium,and low calcium)after 3 days of intervention,and the BMI index after 7 days of intervention between 2 groups(P＞0.05).Conclusion The management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients can reduce the time of diarrhea,improve the severity of diarrhea,and shorten the time to achieve the target feeding,but has no significant change in the incidence of electrolyte abnormalities.

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases. Methods:The two-sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P＜5×10-8).Causal effect estimates were generated using the inverse-variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed. Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease(OR=1.444,95％CI 1.199 to 1.738,P＜0.001)and ulcerative colitis(OR=1.002,95％CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema. Conclusion:Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Objective:To investigate the efficacy of acidified aliphatic ester in the treatment of atopic dermatitis (AD) in mouse models, and to preliminarily explore its mechanisms of action.Methods:Twenty female BALB/c mice aged 6 to 8 weeks were randomly divided into 2 groups: 5 mice in the blank control group were topically treated with absolute ethanol on both ears (14.3 μl per ear) every day, and 15 mice in the model group were topically treated with calcipotriol liniment (14.3 μl per ear) and 20 g/L ovalbumin (25 μl per ear) on both ears every day for 10 consecutive days to establish AD-like mouse models. From day 11, 15 mice in the model group were randomly divided into 3 groups (5 mice in each group), including AD model group, aliphatic ester group, and acidified aliphatic ester group; in the forenoon, all the 3 groups continued to be topically treated with calcipotriol liniment and ovalbumin to maintain AD-like models; in the afternoon, the aliphatic ester group and acidified aliphatic ester group were topically treated with aliphatic ester and acidified aliphatic ester respectively (10 μl per ear), and no treatment was given to the AD model group. Changes in body weight, ear thickness, ear skin lesion scores, and scratching frequency were observed. Ear skin swabs were obtained from the mice on days 10 and 14 for 16S rRNA gene - based microbial diversity tests. On day 14, mice were sacrificed after reflectance confocal microscopy examinations of the ear skin, ear tissues were resected for hematoxylin and eosin staining, mast cell staining, and real-time fluorescence-based quantitative PCR (RT-qPCR), and blood samples were collected for detection of serum IgE levels. One-way analysis of variance was used for analysis of data that met homogeneity of variance criteria, and least significant difference- t test for multiple comparisons. Results:On day 14, the severity of mouse ear lesions was the highest in the AD model group, followed in turn by the aliphatic ester group, acidified aliphatic ester group, and blank control group; compared with the AD model group, the acidified aliphatic ester group showed significantly decreased mouse ear thickness ( F = 897.50, P < 0.001), skin lesion scores ( F = 268.80, P < 0.001), scratching frequency ( F = 64.36, P < 0.001), and epidermal thickness ( F = 256.20, P < 0.001). In addition, RT-qPCR indicated that the expression of inflammatory factors such as interleukin (IL) -33, thymic stromal lymphopoietin, IL-4, and tumor necrosis factor-α in lesional areas, and the degree of mast-cell infiltration were all significantly lower in the acidified aliphatic ester group than in the AD model group ( F = 3.38, 8.70, 41.73, 44.30, 134.30, P = 0.049, = 0.001, < 0.001, < 0.001, <0.001, respectively). Microbial diversity tests showed that the acidified aliphatic ester treatment could inhibit the colonization of Staphylococcus spp. in the ears of AD-like mouse models, and the Shannon index and Simpson index significantly differed among the 4 groups ( F = 9.00, 7.92, P = 0.001, 0.002, respectively) . Conclusion:Acidified aliphatic ester could improve skin lesions of AD-like mouse models, possibly by regulating immunity, suppressing inflammation, and restoring skin microecological diversity.

Objective:To explore the correlation between lateral violence, leadership empowering, psychological capital and work alienation among nurses in Oncology Department.Methods:From July to September 2022, a survey was conducted on 327 nurses of Oncology Department in Jiangsu Province using the Nurse Lateral Violence Scale, Chinese version of Empowering Leadership Scale, Chinese version of Psychological Capital Questionnaire and Nurse Work Alienation Questionnaire. The PROCESS program was used to analyze the moderated mediation model.Results:The lateral violence of nurses in Oncology Department had a positive predictive effect on work alienation, and the difference was statistically significant (β=0.339, P<0.01) . Leadership empowering had a partial mediating effect on the correlation between lateral violence and work alienation with a statistical difference, the effect value was 0.071, accounting for 20.94% of the total effect. Psychological capital had a moderating effect on the second half of the mediating effect of leadership empowering, and the difference was statistically significant (β=-0.360, P<0.01) , and the impact of lateral violence on work alienation increased with the increase of psychological capital level. Conclusions:The lateral violence among nurses in Oncology Department can affect work alienation through leadership empowering. The mediating model of psychological capital regulating the correlation between leadership empowering and work alienation is established.

Objective: To investigate the coverage of rotavirus vaccination among children under five years in Xiuzhou District of Jiaxing City, so as to provide insights into rotaviral diarrhea control. Methods: The rotavirus vaccination data of children aged two months to five years were extracted from the vaccination clinics of eight township hospitals and community health service centers through the Zhejiang vaccination information system. The coverage of rotavirus vaccination was analyzed among children with different genders, ages, types of vaccines and doses of vaccination. Results: Totally 32 752 children were included, and the coverage of rotavirus vaccination was 47.09%. The coverage of rotavirus vaccination was significantly higher in boys than in girls ( 47.65% vs. 46.46%, P<0.05 ), and a higher vaccination rate was seen in children with local household registration than in those without ( 56.76% vs. 38.75%, P<0.05 ). The vaccination rates of monovalent and pentavalent rotavirus vaccines were 36.90% and 10.18%, respectively. Totally 26 982 doses of rotavirus vaccines were vaccinated, with a mean dose of ( 0.84±1.02 ) per capita, and the vaccination rates of one, two and three doses were 20.75%, 17.37% and 8.96%, respectively. The median age was 6.00 months ( interquartile range, 3.00 months ) among children vaccinated with the first dose. Conclusions The coverage of rotavirus vaccination and full-dose vaccination are low among children under five in Xiuzhou District, with monovalent rotavirus vaccines predominant. Intensified rotavirus vaccination is therefore recommended.

Objective:To investigate the drug resistance of patients with acquired immunodeficiency syndrome (AIDS) who failed antiviral therapy.Methods:A total of 156 AIDS patients with antiviral therapy failure at the Sixth People′s Hospital of Zhengzhou from October 2017 to December 2018 were selected. The human immunodeficiency virus (HIV)-1 ViroSeq? genotyping method was used for the detection of HIV resistance, and Stanford University HIV drug resistance database (http: ∥hivdb.stanford.edu/) was used for testing results comparison.Results:Among the 156 AIDS patients with antiviral therapy failure, 122(78.21%) developed drug resistance. One hundred and six (67.95%) cases were multi-resistant to nucleoside reverse transcriptase inhibitor (NRTI), among which, 104 (66.67%) were resistant to lamivudine, emtricitabine and abacavir. One hundred and eighteen (75.64%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI), and 118 (75.64%) were multi-resistant to efavirenz and nevirapine. And seven (4.49%) were resistant to protease inhibitor (PI). There were 16 resistant sites for NRTI, with 87 (71.31%) most frequent M184V/I mutations. There were 13 resistant sites for NNRTI, with 49 (40.16%) K103N/R mutations. There were 11 resistant sites for PI, with 49 (40.16%) A71V/T mutations. The antiviral drugs lamivudine and emtricitabine were moderately and highly resistant in 102 (83.61%) cases, efavirenz and nevirapine were moderately and highly resistant in 117 (95.90%) cases. Once drug resistance developed, these drugs were likely to be moderate or high resistance. There were 29 (23.77%), 48 (39.34%), and five (4.10%) cases were resistant to zidovudine, tenofovir and lopinavir/ritonavir, respectively. The resistance barrier of these drugs was relatively high.Conclusion:The incidence of drug resistance in patients with AIDS treatment failure is high, and multi-drug resistance is serious with various sites of drug resistance.

Objective:To quantitatively evaluate the energy loss (EL) and vortex characteristics in the left ventricle by vector flow mapping (VFM) technique in heart failure patients with mid-range ejection fraction (HFmrEF) and reduced ejection fraction (HFrEF).Methods:One hundred and five patients in Qilu Hospital of Shandong University from October 2016 to November 2017 with heart failure and left ventricular ejection fraction (LVEF)<50% were enrolled and divided into HFmrEF Group (LVEF40%~<50%, 56 cases) and HFrEF group (LVEF<40%, 49 cases). Another 32 healthy people at the same period were matched as control group. The EL, vortex area and circulation of isovolumic relaxation phase (IVR), rapid filling phase (RFP), atrial contraction phase (ACP), isovolumic contraction phase (IVC) and rapid ejection phase (REP) in the left ventricle was measured by VFM technique.Results:The EL in HFmrEF group and HFrEF group was lower than that in the control group. In ACP, the EL was gradually decreased among the control group, HFmrEF group and HFrEF group( P<0.05). In ACP, the vortex area and circulation was larger in heart failure patients than those in the control group, and gradually increased from control group, to HFrEF group( P<0.05). Positive correlation between EL and E/e ′ was evidenced in the RFP ( r=0.524, P< 0.001). While in ACP, there was a positive correlation between EL and A peak ( r=0.492, P<0.001), and a negative correlation between EL and vortex area ( r=-0.235, P=0.040). Conclusions:VFM can be applied to evaluate the EL in left ventricle. The EL in the left ventricle of patients with HFmrEF and HFrEF is significantly lower than that in control group. El is correlated with cardiac systolic and diastolic function and vortex area.

Objective To understand the application value of spacial clusters detection of human schistosomiasis epidemic,based on small scale level in heavy mountainous and hilly endemic areas, Songzi County,Hubei Province,China. Methods Positive results of human serological detection antibody titer equal or above 80,and positive schistosomiasis cases of fecal examination from 2016 to 2018 as research object in Songzi County.The flexible irregular space scan statistics was used to analyse the spatial clustering analysis of human schistosomiasis epidemic in the heavy mountainous and hilly endemic areas, setting parameter K=2 ,K=6 or K=10, respectively,based on small scale of village level in Songzi County. Results There was none positive schistosomiasis cases of fecal examination in Songzi County from 2016 to 2018.The number of human serological detection antibody titer equal or above 80 were  74, 206, 83, from 2016 to 2018，respectively.There was spatial clusters of positive of human serological detection antibody titer equal or above 80 for schistosomiasis cases in the county from 2016-2018. Areas of flexible irregular space scan statistic in cluster detection changing with the change of different K values. Under different parameters of flexible irregular space scan statistic results show that the most likely cluster of 40 endemic villages in three towns,inculding Laocheng town,Chendian town and Wangjiaqiao town were the prominent. Conclusion There are spatial clusters of human schistosomiasis based on small scale of village level by flexible irregular space scan statistic in mountainous and hilly endemic areas, Songzi County,Hubei Province.Therefore,the monitoring and control of schistosomiasis should be consolidated in the future,in order to achieve schistosomiasis elimination in Hubei Province at an early date.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.