OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

OBJECTIVE: This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer. METHODS: Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study. RESULTS: Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of α-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol. CONCLUSION Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition (EMT) signaling pathways.

Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.

Objective To analyze the values of serum tumor necrosis factor-α stimulated gene 6 protein (TSG-6) and type ⅩⅥ collagen (col-16) in predicting the prognosis of patients with ulcerative colitis (UC). Methods A total of 160 patients with UC were enrolled as UC group, another 160 volunteers were selected as control group, and the levels of serum TSG-6 and col-16 were compared between the two groups. According to the modified Mayo scoring criteria, patients in the UC group were divided into mild group (n=63), moderate group (n=52), and severe group (n=45), and the levels of serum TSG-6 and col-16 were compared among the three groups. Based on the colonoscopy follow-up results, patients in the UC group were divided into good prognosis group (n=121) and poor prognosis group (n=39), and the levels of serum TSG-6 and col-16 were compared between the two groups. Spearman correlation analysis was used to explore the correlations of serum TSG-6 and col-16 with the modified Mayo score. Logistic regression analysis was used to investigate the impact of serum TSG-6 and col-16 on the prognosis of patients in the UC group. Receiver operating characteristic (ROC) curve was used to assess the values of serum TSG-6 and col-16 in predicting the prognosis of patients in the UC group. Results The levels of serum TSG-6 and col-16 in the UC group were significantly higher than those in the control group (P < 0.01). The levels of serum TSG-6 and col-16 in the moderate and severe groups were significantly higher than those in the mild group, and the levels of serum TSG-6 and col-16 in the severe group were significantly higher than those in the moderate group (P < 0.01). The levels of serum TSG-6 and col-16 in the poor prognosis group were significantly higher than those in the good prognosis group (P < 0.01). Spearman correlation analysis showedthat serum TSG-6 and col-16 were positively correlated with the modified Mayo score (r=0.691, P < 0.05; r=0.635, P < 0.05). Logistic analysis results showed that serum TSG-6 and col-16 were risk factors for poor prognosis (P < 0.001). ROC curve analysis showed that the areas under the curve for predicting poor prognosis in patients with UC were 0.773 and 0.765 for serum TSG-6 and col-16, respectively. Conclusion The levels of serum TSG-6 and col-16 are abnormally elevated in patients with UC, and there is a certain correlation of the two indexes with the severity and prognosis of disease, and the two indexes can be used as predictors of poor prognosis.

Objective To investigate the effects of tegafur, gimeracil and oteracil potassium combined with oxaliplatin on gastric motility-related hormones, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in elderly patients with gastric cancer. Methods A total of 128 elderly patients with gastric cancer were selected as the study subjects and randomly divided into control group (n=64) and observation group (n=64). The control group was treated with tegafur, gimeracil and oteracil potassium, while the observation group received tegafur, gimeracil and oteracil potassium combined with oxaliplatin. Gastric motility-related hormones [motilin (MTL) and vasoactive intestinal peptide (VIP)], MMP-2, MMP-9, tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9)], clinical efficacy and occurrence of adverse reactions were observed in both groups. The correlations of gastric motility-related hormones with the levels of MMP-2, MMP-9 and tumor markers were analyzed. Results After treatment, MTL levels in both groups were significantly lower, while VIP levels were significantly higher compared to before treatment. Additionally, the observation group had significantly lower MTL and higher VIP levels compared to the control group (P < 0.05). After treatment, the levels of MMP-2, MMP-9, CEA, CA125 and CA19-9 were significantly reduced in both groups compared to pretreatment levels, with the observation group showing significantly lower levels than the control group (P < 0.05). The total effective rate in the observation group was 70.31%, which was significantly higher than the 53.13% in the control group (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). A negative correlation was observed between MTL and MMP-2, MMP-9, CEA, CA125 as well as CA19-9 (P < 0.05), while VIP showed a positive correlation with MMP-2, MMP-9, CEA, CA125 and CA19-9 (P < 0.05). Conclusion The combination of tegafur, gimeracil and oteracil potassium and oxaliplatin is effective and safe for the treatment of elderly patients with gastric cancer. MTL, VIP, MMP-2, MMP-9, CEA, CA125 and CA19-9 are interrelated in the development of gastric cancer in elderly patients.

In this study, in order to overcome the shortcomings of the current methods used to identify Bifidobacterium animalis, such as long time, complicated operation and low adaptability of experimental environment, specific primer probes were designed based on ERIC-PCR technology to identify and detect B.animalis.Based on the genomic DNA of B.animalis HP-B1124, the ERIC-PCR reaction conditions of B.animalis HP-B1124 were optimized, and the ERIC-PCR fragments were obtained one by one and sequenced.Two pairs of specific primer probes were designed.The accuracy, specificity, limitation and universality of the two pairs of primer probes were evaluated, and the two pairs of specific primer probes were used for testing the products containing B.animalis in the commercially published formula.The two pairs of specific primer probes designed in this study could be used for identified strains of B.animalis more simply, quickly and targeted.This method has optimized the current relatively traditional methods of pure culture and plate counting identification of B.animalis, and has solved the high requirements of SNP genotyping technology and real-time fluorescence quantitative PCR method for experimental equipment and reagents in the identification of B.animalis to a certain extent.It has the characteristics of low cost, high specificity and earn a broad market development prospect.

Objective To analyze the current status of application of clinical decision support system(CDSS)in nursing field,and to provide reference for related research in China.Methods Literature on CDSS in nursing published in the Web of Science core database from January 1,2009 to April 10,2022 was searched.CiteSpace and VOSviewer software were used for visual analysis of journals,countries,key words,etc.Results A total of 2030 literatures were included,and the overall number of publications and citations showed an upward trend.PLoS One was the journal with the highest number of publications,the United States had the highest number of publications,strategies,challenges and burdens were the key words that appeared in recent years.The field had changed from exploratory clinical research to clinical practice,and the challenges and burdens encountered by CDSS in clinical practice and the countermeasures were the current research hotspots.Conclusion Currently,the application of CDSS in clinical care is in its infancy and still faces many challenges,and there is an urgent need for more high-quality research to improve the quality of clinical care and the efficiency of nurses,and to reduce the burden of work.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To summarize the clinical characteristics, imaging features, diagnosis, treatment and prognosis of pulmonary actinomycosis in children.Methods:The clinical data of a child with pulmonary actinomycosis who was hospitalized in Children′s Hospital, Zhejiang University School of Medicine in December 2019 was retrospectively analyzed. The related literature published from January 1975 to January 2020 was retrieved from Wanfang, CNKI and PubMed databases with "pulmonary" or "thoracic" and "actinomycosis" and "pediatric" or "children" or "child" as the keywords. And the characteristics of pediatric pulmonary actinomycosis were summarized based on the literature review.Results:The patient was a boy aged 12 years and 6 months. He was admitted due to cough and chest pain for more than 20 days, with fever on the first three days. The chest CT scan in local hospital found inflammatory lesions in the right middle lobe, which was also suspected to be cavitation. The flexible bronchoscopy showed congestion and edema of bronchial mucosa in the right middle lobe, and bronchoalveolar lavage fluid smear was positive for acid-fast bacilli DNA, although both purfied protein derivatives tuberculin test and T-spot were negative. During the hospitalization, the child had persistent cough and chest pain, but no fever. Pathogen metagene sequencing of the bronchoalveolar lavage fluid detected Actinomyces (sequence number: 222) and Grevini Actinomycetes (sequence number: 185). The boy received intravenous cefoperazone sulbactam sodium for 2 weeks followed by oral amoxicillin clavulanate potassium for 6 weeks. Until April 2020, his clinical symptoms completely relieved, and the pulmonary lesions were significantly absorbed on the latest chest CT scan. Eight articles and 62 children with pulmonary actinomycosis were reported, but no related reports were retrieved from CNKI and Wanfang databases. The youngest case was 27 months old. The clinical presentations of this disease were nonspecific. The main symptoms included chest wall masses (8 cases), cough (23 cases), pain (chest, back, shoulders and armpits) (24 cases), fever (25 cases), weight loss (26 cases), etc.Conclusions:The clinical manifestations and imaging features of pediatric pulmonary actinomycosis are nonspecific, therefore it could easily be misdiagnosed. For children with pneumonia of unknown etiology and failing to respond to routine antibiotics, the pathogen metagene sequencing of the bronchoalveolar lavage fluid will be helpful for diagnosis. With appropriate course of antibiotic treatment, the prognosis is good in most cases.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.