OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.

OBJECTIVES: To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation. METHODS: The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation. RESULTS: The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated. CONCLUSIONS Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/pathology* ; Curcumin/pharmacology* ; Humans ; Liver Neoplasms/pathology* ; Network Pharmacology ; Tumor Suppressor Protein p53/metabolism*

【Objective】 To investigate the main causes of blood donor deferral in domestic blood center. 【Methods】 The causes of donor deferral were classified into 12 categories as previous medical history, drug use, alcohol consumption, menstrual period, underweight, abnormal blood pressure, abnormal body temperature, abnormal hemoglobin (Hb), lipemic blood, positive hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) and others according to the comparison indicators of Asia-Pacific Blood Network (APBN) and the national standard Blood Donor Health Examination Requirements. The relevant data of the top 3 causes of donor deferral, voluntarily reported by the members of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions from 2014 to 2019, were collected and a histogram was generated. 【Results】 The median donor deferral rate of 20 domestic blood centers from 2014 to 2019 was 12.14%, with the lowest at 0.18% and highest at 32.32%, respectively. The top three causes for donor deferral were elevated ALT, abnormal Hb and abnormal blood pressure in year 2014, 2015, 2018 and 2019; elevated ALT, lipemic blood and abnormal blood pressure in 2016; elevated ALT, abnormal Hb, and lipemic blood in 2017. 【Conclusion】 The main causes of donor deferral were elevated ALT, abnormal Hb, abnormal blood pressure and lipemic blood.

Immunotherapy combined with targeted therapy can benefit the survival of patients with unresectable hepatocellular carcinoma. Atezolizumab combined with bevacizumab has achieved remarkable efficacy in patients with advanced hepatocellular carcinoma, but the efficacy of conversion therapy in patients with unresectable hepatocellular carcinoma still needs more evidences. The authors report the clinical efficacy of a case of unresectable hepatocellular carcinoma with hepatitis B virus related liver cirrhosis who was treated with immunotherapy plus targeted therapy combined with local treatment. Results show a good effect in patient without tumor recurrence after postoperative 9 months.

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Objective:To explore the application effect of early warning model of chemotherapy complications in nursing care of non-small cell lung cancer during chemotherapy.Methods:By using convenient sampling method, 106 patients with non-small cell lung cancer treated by chemotherapy in the Thoracic Surgery Department of the First Affiliated Hospital of Zhengzhou University from January 2016 to February 2019 were selected as the study objects. According to the time of admission, they were divided into the control group ( n=52) and the observation group ( n=54) . The control group was given routine nursing care during chemotherapy, while the observation group was given nursing care through early warning model of chemotherapy complications during chemotherapy. Hamilton Anxiety Scale (HAMA) , Hamilton Depression Scale (HAMD) and European Organization for the Research and Treatment of Cancer QLQ-C30 (EORTCQLQ-C30) were used to compare the intervention effect of the two groups, and the incidence of complications during chemotherapy was counted. Results:The total incidence of complications was 26.92% (14/52) in the observation group and 46.15% (24/52) in the control group, the difference was statistically significant (χ 2=4.147, P<0.05) . Three months after the intervention, HAMA (9.87±4.25) and HAMD (15.54±3.58) in the observation group were lower than those in the control group; the differences were statistically significant ( t=4.738, 8.296; P<0.05) . The functional score, symptom score, overall quality of life score and single measurement item score of the observation group were higher than those of the control group with statistical differences ( P<0.05) . Conclusions:During chemotherapy for non-small cell lung cancer, nursing through the early warning model of chemotherapy complications can reduce the incidence of chemotherapy complications, alleviate the negative emotions of patients, and improve the quality of life, which is worthy of clinical application.

Objective To analyze the clinicopathological features and prognosis of patients in endometrial cancer with bone metastases. Methods A retrospective review of medical records was performed to analyze patients with endometrial cancer who developed bone metastases at Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017, including patients with bone metastases at the diagnosis of endometrial cancer and at recurrence of endometrial cancer. The patient′s clinicopathological features, bone metastasis characteristics, treatment process and prognoses were also analyzed. Results The incidence of bone metastasis of endometrial cancer in PUMCH from 2004 to 2017 was 0.57% (14/2 458). (1) General clinical pathological features: the median age of the 7 patients with bone metastases diagnosed at the time of initial diagnosis was 50 years old, and the main pathological type was endometrioid carcinoma (n=5). The median age of the other 7 patients was 57 years old, with no significant difference comparing to the former groups (P=0.559). (2) The majority site of bone metastasis in endometrial cancer were discovered in pelvic bones, followed by the tibia. (3) Treatment: according to the staging of endometrial cancer, a comprehensive treatment based on surgery was performed, and one patient with isolated bone metastases underwent resection of bone metastasis. (4) Prognosis: nine out of the 14 patients died during the follow-up period. The median over all survival time was 25.5 months (range: 7.7-258.0 months). The median survival of population after diagnosis of bone metastases was 15.0 months (range: 3.0-51.0 months). The survival rate of endometrial cancer at 1-year after diagnosis of bone metastasis was 71.4%. The 2-year survival rate was 40.8%. (5) No independent prognostic factors affecting survival was found (P>0.05). Conclusions The incidence of bone metastasis in endometrial cancer is less than 1%. Bone metastasis could occur at the diagnosis of endometrial cancer or recurrence of endometrial cancer. Bone metastasis suggests a poor prognosis. There is no standard follow-up and treatment protocols so that individualized treatment is needed.

Objective To explore the characterization of thyroid stimulating hormone receptor(TSHR) gene mutational spectrum in children with hyperthyroidism from Guangzhou. Methods Ninety children were diagnosed with hyperthyroidism from July 2009 to July 2014 in our institute. Their median age at diagnosis was(7.5± 3.4) years, and there were 28 males and 62 females. Mutational analysis were performed by performing polymerase chain reaction (PCR) and DNA direct sequencing of exon 10 of TSHR gene. TSHR gene mutations from 50 unrelated healthy children were served as controls. The correlation between TSHR gene and hyperthyroidism in children was explored. Results A total of 3 mutations were identified in ninety children who were diagnosed with hyperthyroidism, one synonymous mutations(p.V614V), and two missense mutations( p. R707W and p. D727E). Mutation of p. V614V do not change amino acid and do not influence the structure and function of TSHR, no pathogenicity. p.R707W is a SNP associated with human cancers. The frequency of C allele of the D727E in children with hyperthyroidism was 86.7%, while 55.0% in the controls, significant different between the children with hyperthyroidism and the controls( P＜0. 01). In this study, a very high association between the D727E SNP and hyperthyroidism ( OR=18. 86, P＜0. 01) was found. Conclusion Three different mutations of TSHR gene exon 10 were identified in 90 children with hyperthyroidism, (c.1842A＞G,p.V614V、c.2119C＞T,p.R707W、c.2181G＞C,p.D727E), there were association between p.D727E and hyperthyroidism, nor p. V614V and p. R707W. Finally, p. D727E may be correlated with hyperthyroidism in children.

Objective? To explore the effects of grading health education model on self-care behavior and health behavior among elderly bronchiectasis patients outside hospital. Methods? From March 2015 to March 2017, we selected 120 elderly bronchiectasis patients at the First Affiliated Hospital of Zhengzhou University by convenience sampling. All of the patients were divided into control group and observation group with the method of the random number table, 60 cases in each group. Control group carried out routine health education. Observation group received the grading health education model dividing health education into three stages and pushing education content by WeChat;a total of 12 times of health education were implemented. The interventional cycle was three months between two groups. The Appraisal Self-Care Agency Scale-Reviewed (ASAS-R-C) and the Self-Rated Abilities for Health Practices Scale (SRAHP) were used to assess the self-care behavior and health behavior of patients outside hospital. Results? Before intervention, there were no statistical differences in the score of ASAS-R-C and SRAHP (P＞ 0.05). After intervention, the dimension scores of ASAS-R-C, SRAHP and the total score were higher than those before intervention with statistical differences (P＜0.05). After intervention, the scores of self-care goal, self-care skill, the total score of ASAS-R-C, health responsibility, sport management and the total score of SRAHP of intervention group were (25.62±2.18), (24.52±2.41), (74.72±6.27), (24.78±2.75), (25.21±2.16) and (98.35±8.16) higher than those of control group with statistical differences (P＜ 0.05). Conclusions? Grading health education model is propitious for elderly bronchiectasis patients to clear the nursing goal, improve nursing skills, enhance their health responsibility and improve their sport management abilities which is worthy of popularization and application.

Objective: To establish a new standard for the quality evaluation of Schisandrae chinensis Fructus. Methods: On the basis of the 2015 edition pharmacopoeia standard of Schisandrae chinensis Fructus, some testing items including the characteristic chro-matogram (HPLC) and total lignans content (UV) were established. Results: With schizandrin as the reference material, the HPLC specific chromatograms of Schisandrae chinensis Fructus including 7 characteristic peaks were established. The content of total lignans in Schisandrae chinensis Fructus was not less than 1. 8% with schizandrin as the standard. Conclusion: The proposed quality evalua-tion standard is more comprehensive and reproducible. It can provide a more scientific evaluation tool for the quality evaluation of Schisandrae chinensis Fructus and its related preparations.