ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Objective The purpose of writing the"Expert consensus on the prevention and control of intracranial hypertension in adult critical illness"(here in after referred to as the"Consensus")aimed to standardize the nursing work related to the prevention and control of elevated intracranial pressure in adult critical illness,and prevent the occurrence of complications such as cerebral herniation.Methods Guided by evidence-based practice,domestic and foreign databases were searched for guidelines,expert consensuses,systematic evaluation,evidence summaries,and original research related to increased intracranial pressure.The search period is from database establishment to March 2024.The high-quality evidence and suggestions in the field was evaluated,extracted,and summarized to form a preliminary consensus.27 experts were invited to conduct 2 rounds of expert inquiry and 8 experts were invited to conduct 2 expert discussion meetings,to revise and improve the content of the initial draft,and to ultimately form a final consensus.Results The effective response rates for both rounds of inquiry questionnaires were 100％,with expert authority coefficients of 0.884,judgment coefficients of 0.964,and familiarity levels of 0.804.The Kendall harmony coefficients for 2 rounds of inquiry were 0.107 and 0.083(P＜0.01),respectively.The consensus includes 4 aspects,including identification,monitoring,prevention and control strategies,emergency treatment and care for increased intracranial pressure.Conclusion This"Consensus"has strong scientific validity and can provide reference basis for nurses to carry out prevention and control of intracranial pressure increase.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

OBJECTIVE: To test the reliability and validity of the Chinese version of adverse childhood experiences international questionnaire (ACE-IQ) in Chinese parents of preschool children. METHODS: The parents of preschool children in 6 kindergartens in Tongzhou District of Beijing were selected by stratified random cluster sampling, and the Chinese version of ACE-IQ after translation and adaptation was used for survey online. The collected data were randomly divided into two parts. One part of the data (n=602) was used for exploratory factor analysis (EFA), to screen items and evaluate structural validity, and then form the final Chinese version of ACE-IQ. The other part of the data (n=700) was used for confirmatory factor analysis (CFA), criterion validity analysis and reliability analysis. At the same time, experts investigation method was used to evaluate the content validity of the final Chinese version of ACE-IQ. RESULTS: After deleting four items of collective violence, the Chinese version of ACE-IQ with twenty-five items indicated good structural, criterion and content validity. Analysis results showed that the Chinese version of ACE-IQ presented a seven-factor model dimension, namely emotional neglect, physical neglect, family dysfunction, family violence, emotional and physical abuse, sexual abuse and violence outside the home, and the total score of the binary version of ACE-IQ Chinese version was positively correlated with the total score of childhood trauma questionaire-28 item short form (CTQ-SF, r=0.354, P < 0.001) and the center for epidemiological studies depression scale (CES-D, r=0.313, P < 0.001) respectively. Results from five experts showed that the item-level content validity index (I-CVI) of 25 items was between 0.80 and 1.00, and the average of all I-CVIs on the scale (S-CVI/Ave) of the scale was 0.984. At the same time, the internal consistency (Cronbach's α coefficient) of the whole scale was 0.818, and the split-half reliability (Spearman-Brown coefficient) was 0.621, which demonstrated good reliability. CONCLUSION This study has formed a Chinese version of ACE-IQ with 25 items and 7 dimensions, which has good reliability and validity among the parents of preschool children in China. It can be used as an evaluation instrument for measuring the minimum threshold of the adverse childhood experiences in the parents of preschool children in the cultural background of China.
Humans ; Child, Preschool ; Adverse Childhood Experiences ; Reproducibility of Results ; Parents/psychology* ; Surveys and Questionnaires ; China ; Psychometrics/methods*

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; TOR Serine-Threonine Kinases/metabolism* ; Fluorouracil/pharmacology* ; Cell Proliferation ; Autophagy ; Colorectal Neoplasms/drug therapy*

According to the current cervical cancer screening strategy and the World Health Orgnization cervical cancer diagnosis/screening guidelines, gene methylation will be included in the new guidelines in the future. However, the value of detecting DNA methylation at specific sites in the clinical specimens during the cervical cancer treatment remains to be discussed. This article summarised the role of DNA methylation in the development of cervical cancer and discusses the potential clinical application of methylation detection in the management of high-risk human papillomavirus (hrHPV) positive female patients. It is believed that methylation test can not only be used for the preliminary classification of hrHPV positive female patients, but also for the secondary triage of female patients with slight cytological abnormalities to determine the high risk of cervical intraepithelial neoplasia 3(CIN3) or cancer. It can also be used for the withdrawal test of women in the screening program to support the management of CIN.

Objective To explore the expression and distribution characteristics of vascular endothelial growth factor-B(VEGF-B) in diencephalon and brainstem of Yak’s brain tissues, and to investigate the associations between its expression and hypoxia adaptation. Methods Five healthy yaks were selected, and the brain tissues were divided and collected according to the gross anatomical structure of the brain, including pituitary, thalamus, hypothalamus, oblongata and pons. The characteristics of expression and location of VEGF-B in different regions of Yak’s brain tissues were detected by Real-time PCR, Western blotting and immunohistochemical techniques. Results The results showed that the highest expression level of VEGF-B mRNA of yak brain tissue was in the pituitary, and the content was significantly higher than that found in other parts of the brain(P<0. 05). Following the expressions were in the hypothalamus, thalamus and medulla oblongata, while the lowest expression level was in pons. The expression level of VEGF-B protein in Yak’s brain tissue was similar to the mRNA expression level except that the thalamus was higher than that of hypothalamus. The result of immunohistochemistry showed that VEGF-B protein-positive substances were mainly distributed in the cytoplasm of various types of cells. Among them, the positive staining of VEGF-B was mainly concentrated in eosinophils of pituitary. The positive staining of VEGF-B was mainly concentrated in pleomorphic cells of thalamus and hypothalamus. The distribution of VEGF-B protein-positive substances were mainly focused in nerve cell body of medulla oblongata and pons. Conclusion VEGF-B protein is expressed in both diencephalon and brainstem of yak, which may be closely related to its functions of anti-apoptosis, "survival factor" and angiogenesis. However, the specific mechanism of its neuroprotective effect on Yak brain under hypoxic environment needs to be further studied. The difference of expression in different regions may be related to the tissue specificity and function in different regions of the brain.

Objective To observe the clinical efficacy and safety of bevacizumab in the treatment of platinum-resistant ovarian cancer,tubal cancer,peritoneal carcinoma cancer.Methods Patients with platinum resistance ovarian cancer,tubal cancer and peritoneal carcinoma cancer treated with bevacizumab were in included into treatment group.Patients with platinum-resistance in ovarian cancer,tubal cancer and peritoneal carcinoma cancer who received docetaxel chemotherapy during the same period were included into control group.The treatment group was given bevacizumab 5 mg·kg-1 by intravenous infusion once every 2 weeks,and the first intravenous infusion lasted for 90 min,with a total of 4 times of chemotherapy.The control group was given docetaxel 70-75 mg·m-2 by intravenous infusion,once every 3 weeks,1 h each time,a total of 4 times of chemotherapy.The clinical efficacy after chemotherapy,the levels of serum squamous cell carcinoma antigen(SCC-Ag),malignant tumor-related substance group(TSGF),cytokeratin 19 fragment(CYFRA21-1),the changes of tumor markers,immune indexes and the occurrence of adverse drug reactions were compared between the two groups.Results There are 70 cases in treatment group and 50 cases in control group.After four rounds of chemotherapy,the total effective rates of treatment group and control group were 47.14％(33 cases/70 cases)and 30.00％(15 cases/50 cases),with statistically significant difference(P＜0.05).After chemotherapy,the SCC-Ag levels in treatment group and control group were(3.10±1.05)and(5.50±1.95)mg·L-1;TSGF levels were(30.20±9.94)and(56.70±10.45)U·mL-1;CYFRA21-1 levels were(1.03±0.45)and(2.10±0.99)mg·L-1;carcinoembryonic antigen(CEA)levels were(66.81±48.74)and(89.18±56.08)ng·mL-1;the tumor markers CA199 were(110.26±51.36)and(124.13±53.80)U·mdL-1;the gastric cancer antigen(CA724)were(14.70±9.72)and(20.54±18.51)U·mL-1;the CD3+levels were(72.45±9.45)％and(67.10±10.25)％;the CD4+levels were(48.49±9.15)％and(39.56±6.77)％;the CD8+levels were(20.18±3.85)％and(24.02±4.45)％,the differences were all statistically significant(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between the two groups(P＞0.05).Conclusion Bevacizumab is more effective than docetaxel in the treatment of platinum-resistant ovarian cancer,tubal cancer,peritoneal carcinoma cancer.