To observe BAG-1, EGFR, and PARP-1 expressions in invasive breast cancer and its correlation with clini-cal pathological indicators, as well as to evaluate their clinical significance. Methods:The BAG-l, EGFR, and PARP-1 expressions in a tissue microarray of invasive breast cancer and peritumoral tissues were detected through immunohistochemical staining. The clinical and pathological significance of BAG-1, EGFR, and PARP-1 were evaluated. Results:The BAG-1, EGFR, and PARP-1 expression lev-els are higher in invasive breast cancer tissues than in peritumoral tissues (P<0.05). BAG-1 expression in invasive cancer tissues is not related to age, tumor site, lymph node metastases, and clinical TNM staging of patients, but is related to size, grade, ER, PR, and HER-2 expressions and molecular subtype (P<0.05). EGFR expression is related to size, clinical TNM staging, and molecular subtype (P<0.05). PARP-1 expression is related to grade, lymph node metastases, ER, and molecular subtype (P<0.05). BAG-1 expression is not significantly correlated with EGFR and PARP-1 in all cases, but BAG-1 and PARP-1 expressions are positively correlated in tri-ple-negative breast cancer tissues (P<0.05). Results of the univariate analysis revealed that the BAG-1 and PARP-1 expressions and the molecular subtypes are associated with the prognoses of breast cancer patients. Multivariate analysis revealed that BAG-1 and PARP-1 expressions are factors that are independent of the prognosis. Conclusion: BAG-1, EGFR, and PARP-1 overexpressions in human breast tissues suggest that BAG-1, EGFR, and PARP-1 are related to breast cancer development. BAG-1, EGFR, and PARP-1 are poten-tial biomarkers of breast cancer diagnosis and prognosis.

Objective Although principal components analysis profiles greatly facilitate the visualization and interpretation of the multivariate data,the quantitative concepts in both scores plot and loading plot are rather obscure.This article introduced three profiles that assisted the better understanding of metabolomic data.Methods The discriminatory profile,heat map,and statistic profile were developed to visualize the multivariate data obtained from high-throughput GC-TOF-MS analysis.Results The discriminatory profile and heat map obviously showed the discriminatory metabolites between the two groups,while the statistic profile showed the potential markers of statistic significance.Conclusion The three types of profiles greatly facilitate our understanding of the metabolomic data and the identification of the potential markers.

Objective To investigate the clinical efficacy and safety of re-radiotherapy combined with TS-1 (tegafur gimeracil oteracil potassium capsule) in treatment of local recurrent esophageal carcinoma.Methods A total of 63 esophageal carcinoma patients who recurred after the first course radiation treatment admitted to Jiangdu People's Hospital of Yangzhou during January 1,2012 to June 30,2015 were retrospectively analyzed.Twenty-seven of them treated with re-radiotherapy combined with TS-1 were deemed as the research group and 36 of them treated with radiotherapy alone were deemed as the control group based on different treatment.Then the clinical efficacy and adverse reactions of the two groups were compared.Results The objective response rates were 77.8％ (21/27) and 50.0％ (18/36) respectively in the research group and control group,and the difference was statistically significant (x2 =5.048,P =0.025).The median survival time in the two groups were 21.6 months and 13.7 months,the 1-year (74.1％) and 2-year (44.4％) survival rates of the research group were both higher than those of the control group (52.8％ and 30.6％,respectively),and the difference was statistically significant (x2 =6.086,P =0.013).The major adverse effects of the research group and control group during the treatment were radiation oesophagitis (92.6％ vs.80.5％),radiation pneumonia (18.5％ vs.19.4％),myelosuppression (96.3％ vs.77.8％) and gastrointestinal reactions (25.9％ vs.19.4％).Most of them were 1-2 grade,and there were no statistically significant differences (x2 =0.975,P =0.323;x2 =0.009,P =0.926;x2 =2.941,P =0.086;x2 =0.375,P =0.540).Conclusion The treatment of re-radiotherapy combined with TS-1 for local recurrent esophageal carcinoma can improve the efficacy and prolong survival period,and the adverse reactions are tolerable.

Based on the reported inhibitors TH287, 17 five-membered heterocyclopyrimidine derivatives were designed and synthesized by cyclization, scaffold hopping, bioisosterism and molecular docking technology. The bioassays determined by malachite green method demonstrated that the target compounds displayed good inhibitory activity against MTH1. Among them, the IC50 value of 7 compounds was less than 1 μmol/L, suggesting that these compounds may be candidates for further investigation.

OBJECTIVE:To explore an effective method to formulate management-related strategies for off-lable use of drugs by the evidence-based medicine. METHODS:The process of guideline formulation included seven procedures,i.g. establishment ofguideliesformulation workgroup;investigation and selection of the status quo on off-label drug use;identification of the clinical problems;retrieval and evaluation and comprehensing of evidence;applification of GRADE in evidence quality grading;formation of the recommendations consensus;peer review and result publication. And eventually guidelines were formed based on the steps. This study took off-label use of rheumatoid immunoprotective subjects as a case to explore. RESULTS & CONCLUSIONS:Based on the evidence evaluation system and above 7 steps,the methods and process of guideline formulation on off-label use of rheuma-toid immunoprotective subjects that integrated administration,law,clinical medicine,pharmacy subjects were made .The process of guideline formulation fully reflects multidisciplinary characteristics of the workgroup,the advanced nature of the process,the comprehensiveness of evidence ,the rigor of evidence quality grading,and the normalization of consensus. It provides reference in methodology for establishing a comprehensive evidence-based evaluation and management system of off-label use of drugs for all clinical specialist disease. Therefore,this scientific research results may promote the standardization and legalization of the off-label use of drugs management in China.

Objective:To investigate the effect of integrating nursing home service with rehabilitation therapy for persons with senile dementia.Methods:One hundred elderly persons with senile dementia were randomly divided into an observation group and a control group, each of 50. Both groups were given routine nursing care, while the observation group was additionally provided with rehabilitation training. Before and after the intervention, both groups were evaluated using the mini-mental state examination (MMSE), the Barthel index and QOL-AD.Results:After the intervention, the average MMSE, Barthel index and QOL-AD scores of both groups were significantly improved, with the average improvement in the observation group significantly greater.Conclusions:Rehabilitation training can effectively improve the cognitive functioning, performance in the activities of daily living and life quality of persons with senile dementia.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

ObjectiveTo explore the evolution principles of symptoms including deficiency， phlegm and blood stasis， and of the functional near-infrared spectroscopy （fNIRS） cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease. MethodsA total of 497 patients with complaint of memory loss were included， and were divided into subjective cognitive decline （SCD） group （198 participants）， mild cognitive impairment （MCI） group （228 participants） and dementia （AD） group （71 participants）. Neuropsychological evaluation， traditional Chinese medicine （TCM） syndrome investigation， and fNIRS data collection of prefrontal cortex were performed in each group. Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group； logistic regression was used to analyze the influence of TCM syndromes on the incidence of the patients； association rules were used to analyze the TCM syndromes of the patients； the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared. ResultsKidney essence deficiency syndrome was the dominant syndrome in all stages of AD. There were statistically significant differences in the distribution frequency of kidney essence deficiency， phlegm turbidity obstructing orifices， blood stasis obstructing collaterals， qi and blood deficiency， heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes among the three groups （P＜0.01）， and the scores of kidney essence deficiency syndrome among the three groups were statistically significant （P＜0.01）. Logistic regression analysis showed that kidney essence deficiency， and qi and blood deficiency syndromes were the main risk factors for the SCD group （P＜0.05）， phlegm turbidity obstructing orifices syndrome was the main risk factor for the MCI group （P＜0.05）， and heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group （P＜0.05）. The association rule analysis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support （33.33%） in the SCD group， and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support （32.90% and 52.13%） in both the MCI and AD group. The prefrontal fNIRS results showed that the mean ∆HbO₂ concentration in the left dorsolateral prefrontal cortex （LDLPFC） decreased sequentially among the three groups （P＜0.05）， and the mean ∆HbO₂ concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups （r = -0.142， P＜0.05）. Further analysis showed that the mean ∆HbO₂ concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differences among the three groups （P＜0.05）. ConclusionKidney deficiency is the basis of the pathogenesis of AD， and the key brain area damaged is the LDLPFC. Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease， and the syndromes of AD show the evolution law of deficiency and excess as “kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”. The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms， which can be used to assess the degree of cognitive impairment in AD patients.