ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective To investigate the positive detection and epidemic characteristics of enter ovirus(EV),the pathogen of hand-foot-mouth disease(HFMD),in Hangzhou,and to provide scientific basis for formulating prevention and control strategies of HFMD in the future.Methods From January 2016 to December 2022,14 259 positive cases of enterovirus universal nucleic acid detected in Hangzhou Children's Hospital were collected and analyzed retrospectively by age,gender,detection time and other factors.Results The average positive detection rate of EV was 45.48%(14 259/31 354),among which the positive detection rate of boys was 27.20%and that of girls was 18.28%,the difference was statistically significant(P<0.01).The positive detection rate of EV in children of different ages decreased with the increase of age,and the positive detection rate of EV in children under 5 years old accounted for 90.38%of all positive children.Seasonally,enteroviruses were detected throughout the year,but the incidence was high in summer,and the total positive number from May to July accounted for 49.16%of the total detected number.In terms of year,the positive detection rate of EV has shown a downward trend year by year since 2016.Conclusion There are gender differences in enterovirus infection in Hangzhou,and boys are more susceptible to enterovirus infection,especially children under 5 years old need to pay attention to EV protection.In addition,HFMD has a certain seasonality,with a high incidence in summer,and the annual detection rate has declined year by year since 2016,which may be related to the promotion of vaccines and the improvement of health awareness.

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.

Objective:To explore the effect of health education based on theory of planned behavior combined with stepped care model on negative emotion, psychological flexibility and quality of life in patients with lung cancer undergoing chemotherapy.Methods:From October 2020 to December 2021, 108 chemotherapy patients who underwent lung cancer surgery in Affiliated Hospital of Weifang Medical College and had anxiety or depression that scores was greater than 7 in any dimension of the Hospital Anxiety and Depression Scale (HADS) were selected as the study subjects. The study subjects were divided into observation group ( n=46) and control group ( n=48) by random digits table method. Routine care was implemented in the control group. The observation group implemented health education based on the theory of planned behavior combined with stepped care model intervention. The HADS scale was used every 4 weeks to assess negative emotion in both groups. In observation, patients with negative emotion relief stop the next stage of nursing intervention, and patients without relief continue the next stage of higher intensity nursing intervention. Results:Before the intervention, there were no significant difference in the scores of negative emotion, psychological flexibility and quality of life between the two groups ( P>0.05). After intervention, the scores of all dimensions of negative emotion and the total score in the observation group were significantly lower than those in the control group, and the differences had statistical significance ( t=4.86, 3.19 and 4.53, all P<0.05). After the intervention the scores of psychological flexibility and quality of life dimensions and the total score in the observation group were higher than those in the control group, the differences had statistical significance (t values were -6.01--2.89, all P<0.05). After the intervention, there was no significant difference in the remission rate of negative emotions between the clinical observation stage of the observation group and the concurrent control group ( P>0.05). The remission rates of guided self-help, problem-solving therapy, psychological or drug therapy and total negative emotions in the observation group were 38.46%(15/39), 33.33%(8/24), 6/16 and 78.26%(36/46), respectively, which were higher than those in the control group, and the differences had statistical significance ( χ2 values were 7.04 - 13.80, all P<0.05). Conclusions:Health education based on the theory of planned behavior combined with stepped care model can effectively alleviate the negative emotions of lung cancer patients undergoing chemotherapy and improve psychological flexibility and quality of life.

Objective To investigate the prevalence of common enterovirus infections among children in Hangzhou ,2016 .Methods A total of 2977 of throat swabs samples or stool samples from suspected children with enterovirus infection at Hangzhou Children′s Hospital in 2016 were collected . Enterovirus universal nucleic acid ,enterovirus type 71 (EV71) ,Coxsackievirus A (CoxA)16 ,CoxA6 , CoxA4 and CoxA10 were detected by real-time fluorescent quantitative polyoneras chain reaction .The detection positive rates among children with different genders and ages were compared by χ2 test .Results The total enterovirus positive rate of 2977 specimens was 49 .7％ (1480/2977) .Among them ,CoxA6 , EV71 ,CoxA16 ,CoxA4 ,CoxA10 and other enteroviruses accounted for 30 .2％ (447) ,19％ (281) , 10 .2％ (151) ,6 .8％ (101) ,3 .4％ (51) and 30 .3％ (449) ,respectively .Among 1480 enterovirus positive children ,882 cases were male and 598 were female ,with no statistical significance (χ2 = 4 .564 , P=0 .471) .The detection rates of enterovirus in children with hand ,foot and mouth disease (HFMD ) , herpangina and other diseases were 64 .4％ (1051/1632) ,52 .4％ (323/616) and 14 .5％ (106/729) , respectively .The difference among groups was significant (χ2 =503 .387 , P<0 .01) .The prevalences of CoxA6 ,EV71 and CoxA16 in enterovirus-positive HFMD children were 36 .7％ (386) ,25 .3％ (266) and 12 .4％ (130 ) , respectively . The prevalences of CoxA4 , CoxA6 and CoxA10 in enterovirus-positive herpangina children were 20 .1％ (65 ) , 14 .9％ (48 ) and 8 .7％ (28) , respectively , and those of entrovirus ,CoxA4 and CoxA6 in other enterovirus-positive specimens were 59 .4％ (63) ,14 .2％ (15) and 12 .3％ (13 ) , respectively . The enterovirus constituent ratios among children with HFMD , herpangina and other diseases was statistically different (χ2 =399 .758 ,P<0 .01) .The positive rates of enterovirus among different age groups were statistically different (χ2 = 142 .899 , P< 0 .01 );the constituent ratios of enterovirus among different age groups were also statistically different (χ2=106 .160 , P<0 .01) .Conclusion The enterovirus detection rate of CoxA6 is highest ,followed by EV71 and CoxA16 among children in Hangzhou ,2016 .

To investigate the contamination conditions of Campylobacter spp.in duck production chain and its antimicrobial resistance,virulence gene distribution,samples were collected at the duck slaughterhouse according to GB 4789.9-2014.Triplex PCR assay was applied to identify the species of Campylobacter and the recovered Campylobacter strains were tested for the antimicrobial susceptibility against 8 kinds of antimicrobial agents using a broth microdilution method,the susceptibility results were determined according to the NARMS criteria (2011).Subsequently,4 virulence genes were detected by PCR method.The result showed that 187 Campylobacter isolates were obtained from 489 samples,including 160 C.jejuni,130 C.coli and 10 unidentified Campylobacter isolates.The total isolation rate of Campylobacter was 38.24％.The prevalence of Camnpytobacter before slaughtering,at depilation stage,evisceration stage and duck products was 76.33％,5.62％,24.00％,and 0％,respectively.The Campylobacter isolates were most frequently resistant to tetracycline (95.72 ％),followed by resistance to clindamycin(90.91％),the resistance rate of azithromycin (63.64％) was in the middle,the resistance rates of ciprofloxacin(31.02％),gentamicin(34.76％),nalidixic acid (37.43 ％),erythromycin (41.18 ％),chloramphenicol (41.18％) were relatively low.The multi-drug resistance was common among Campylobacter isolates with a rate of 72.19％.The prevalence of adhesion-associated gene cadF,flagellin gene flaA,invasion associated protein gene iamA,toxin regulation gene cdtB was 100％,80.75 ％,71.12％ and 94.65％,respectively.The results indicated that the Campylobacter contamination occurred in the slaughtering procedures of duck,and the antimicrobial resistance of Campylobacter isolates was relatively serious.In addition,the virulence-associated genes were detected widely among Campylobacter isolates.Therefore,the supervision of antimicrobial agents using at rearing stage should be strengthened,along with health management in duck production chain.

Objective To compare the outcomes of endovascular treatment between intracranial large artery atherosclerosis stroke (LAA) and cardioembolic stroke (CE) in Chinese patients with acute anterior circulation ischemic stroke.Methods Patients with acute anterior circulation ischemic stroke treated with the Solitaire stent retriever were enrolled.The patients were divided into either a LAA group or a CE group according to etiological subtype.The outcomes were compared between 2 groups.Multivariable logistic regression analysis was used to determine the independent risk factors for poor outcome (defined as the modified Rankin Scale score ＞2 at 90 d after onset).Results A total of 126 patients were enrolled in the study,including 62 (49.2％) in the LAA group and 64 (50.8％) in the CE group.The proportions of poor outcome at 90 d (59.0％ vs.41.0％;x2 =5.482,P =0.019) and symptomatic intracerebral hemorrhage at 72 h (12.5％ vs.1.6％;Fisher exact test P =0.033) in the CE group were significantly higher than those in the LAA group.Multivariate logistic regression analysis showed that high baseline National Institutes of Health Stroke Scale scores was independently associated with poor outcome (odds ratio [OR] 1.119,95％ confidence interval [CI] 1.026-1.221;P =0.011),good collateral circulation was was independently associated with good outcome (OR 0.227,95％ CI 0.097-0.788;P =0.016),and etiological subtype was not independently associated with outcome (OR 1.280,95％ CI O.454-3.633;P =0.630).Conclusion Etiological subtype is not associated with outcome in patients with acute anterior circulation ischemic stroke treated with the Sofitaire stent retriever.

Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of UGT1 A6 and aspirin response in a cohort of Chinese Han population.Methods A total of 323 ischemic stroke patients consecutively registered in Nanjing Stroke Registry Program from September 2011 to October 2014 were enrolled.Three SNPs (rs6759892,rs2070959 and rs1105879) of UGT1A6 were genotyped in these ischemic stroke patients.Association of genotypes and aspirin response was evaluated by generalized linear model.Indicated with the inhibition rate of platelets,aspirin response was assessed by thromboelastograph.Results The mutation allele (G) of rs2070959 was positively related to platelets inhibition (β =0.084,P =0.010,Pcorrected =0.029),especially in male (β =0.098,P =0.006,Pcorrected =O.019).The dominant models of rs6759892,rs1105879 were also modestly related to aspirin response (P=0.015,Pcorrected=0.046 in both SNPs) in male.Thus the polymorphisms of UGT1A6 showed a relationship with aspirin response,especially in males.Conclusions The results indicated that genetic polymorphism of UGT1A6 might have an effect on individuals' aspirin response,especially in males.These findings can help clinicians to optimize the antiplatelet therapy for ischemic stroke patients.

Objective To explore the clinical application value of serum amyloid A (SAA),C-reactive protein (CRP) and SAA/CRP in early diagnosis of hand-foot-mouth disease (HFMD).Methods The serum levels of SAA and CRP were detected in 873 children with HFMD who were admitted in Hangzhou Children's Hospital from April to December in 2015.And 487 healthy children were enrolled as healthy control group.SAA was measured by nephelometry assay,and CRP was measured by immunoturbidimetry.Variables were compared using Mann-Whitney U test and diagnostic value was measured by using receiver operating characteristic (ROC) curve.Results The median levels of SAA in HFMD group and control group were 330.5 and 4.0 mg/L,respectively,which was statistically different (Z=-29.02,P＜0.01);the median levels of CRP were 10.0 and 1.0 mg/L,respectively,with statistical difference (Z =23.79,P＜ 0.01);and the median SAA/CRP were 23.06 and 2.40,respectively,with statistical difference (Z=-24.79,P＜0.01).In ROC curve comparison,the area under the curve of SAA (0.980) was higher than those of SAA/CRP ratio (0.911) and CRP (0.899) for diagnosing HFMD.When using 10.30 mg/L as the cut off value for SAA according to the ROC curve,the sensitivity was 91.6％ and the specificity was 96.6％.Conclusions Joint detection of SAA and CRP can improve the efficiency in the early diagnosis of HFMD.SAA can provide useful auxiliary information for the diagnosis of HFMD,which is worthy of extensive clinical application.

Stroke has become the leading cause of death in Chinese residents. As the cornerstone of the primary and secondary prevention of ischemic stroke, aspirin can prevent the occurrence and recurrence of ischemic stroke in a certain extent. However, some patients stil have vascular events after taking aspirin regularly or higher platelet aggregation rate. This phenomenon is caled aspirin resistance or aspirin low reactivity. This article reviews the occurrence, detection methods, and treatment measures of aspirin resistance in patients with ischemic stroke.