Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To construct a clinical decision-making ability indicator system based on evidence-based practice for pediatric nursing interns, and to provide a scientific basis for clinical teaching and evaluation.Methods:A method combining literature analysis, Delphi expert consultation, and empirical research was used. Firstly, a systematic search of Chinese and English databases (2018-2023) was conducted. Literature was screened based on the PICO framework and evidence-based data were extracted, resulting in a preliminary system consisting of 4 primary indicators, 12 secondary indicators, and 39 tertiary indicators. Subsequently, the indicators were revised through two rounds of Delphi expert consultation (25 experts with 19-27 years of work experience). The expert authority coefficients (Cr) were 0.898-0.907 and the Kendall's concordance coefficients were 0.351-0.420 ( P<0.001). Finally, the analytic hierarchy process was used to determine the weights, and the reliability and validity were verified through a questionnaire survey (sample size: 30 participants in preliminary survey and 58 participants in formal survey). Results:The constructed indicator system included 4 primary indicators (weights), 13 secondary indicators, and 42 tertiary indicators. The weights of the primary indicators were as follows: knowledge integration ability (0.300), evidence-based practice ability (0.250), clinical judgment ability (0.280), and ethical decision-making ability (0.170). The importance scores of all items exceeded 4.0 points (out of 5 points), and the coefficients of variation were less than 0.20. The reliability and validity tests showed that the Cronbach's α of the overall scale was 0.89, and the intraclass correlation coefficient was 0.88. The cumulative variance contribution rate of exploratory factor analysis was 69.30%. The confirmatory factor analysis demonstrated a good model fit with a comparative fit index of 0.93 and a root mean square error of approximation of 0.05. Conclusions:This indicator system has high scientificity and practicality, and can provide a reference for the standardized cultivation and evaluation of clinical decision-making ability of pediatric nursing interns. In the future, it is necessary to strengthen advanced evidence-based skills training and long-term application effectiveness tracking.

Objective To investigate 5-aminoimidazole-4-carboxamide ribonucleotide formyl transferase/inosine monophos-phate cyclohydrolase(ATIC),a key regulator of metabolism and cell proliferation,to explore its role in glioma proliferation,e-valuate its association with patient prognosis,and elucidate the underlying molecular mechanisms.Methods Using data from The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx),and Chinese Glioma Genome Atlas(CGGA)databas-es,we analyzed differential ATIC expression between tumor tissues and adjacent normal tissues in glioma patients,as well as its correlation with clinical features including pathological grade,isocitrate dehydrogenase(IDH)mutation status,and chromosome 1p/19q deletion.ATIC was knocked down using siRNA transfection.The effect of ATIC on the proliferation of glioma cell lines(LN229,U373,and U251)was evaluated using EdU,CCK-8,and colony formation assays.Furthermore,ATIC overexpression via plasmid transfection was analyzed in conjunction with flow cytometry and Western blotting analysis to assess cell cycle pro-gression and cyclin-related protein expression.Results ATIC expression was significantly elevated in glioma tissues compared to adjacent normal tissues(P＜0.01).Patients with high ATIC expression exhibited shorter overall survival(OS)and were asso-ciated with higher pathological grades,wild-type IDH status,and the presence of chromosome 1p/19q deletion.Compared with U373 and U251 glioma cell lines,LN229 and U87 glioma cell lines demonstrated higher ATIC expression.In siRNA-mediated ATIC knockdown models(siATIC-LN229,siATIC-U373),cell proliferation was suppressed as demonstrated by EdU,CCK-8,and colony formation assays,whereas ATIC overexpression in U251 cells promoted proliferation.Flow cytometry revealed G1-phase arrest and impaired S-phase progression in siATIC-LN229 cells.Conversely,ATIC overexpression in U251 cells decreased G1-phase accumulation and increased S-phase progression.Mechanistically,ATIC knockdown decreased the expression of phos-phorylated Rb(p-Rb),upregulated p21,and downregulated key cyclin-related proteins essential for G1/S transition.In contrast,ATIC overexpression facilitated the G1/S transition through p21 downregulation and enhanced phosphorylation of Rb pro-tein.Conclusion High ATIC expression is associated with poor clinical outcomes in glioma patients and may promote tumor progression through regulation of the p21-Rb signaling pathway.Therefore,ATIC represents a promising biomarker for both clinical diagnosis and prognosis in glioma.

Objective To determine KCNJ14 gene expression in human glioma cells and assess its impact on U251 cell pro-liferation,while exploring the potential mechanism involved.Methods The protein expression levels of KCNJ14 in different hu-man glioma cell lines(U87,U251,SNB19,and LN229)were analyzed by Western blotting.KCNJ14 was knocked down and over-expressed in U251 cells using siRNA and plasmid transfection,respectively.Subsequently,protein expression levels,cell prolif-eration capacity,and the regulation of cell cycle related proteins were measured in each group.The association between KCNJ14 mRNA expression and clinical survival prognosis in glioma patients was evaluated through statistical analysis of public databas-es.Results KCNJ14 protein expression varied across different human glioma cell lines,with the highest level observed in U251 cells.Inhibition of KCNJ14 suppressed U251 cell proliferation and impaired cell cycle progression.Bioinformatics analysis re-vealed that KCNJ14 mRNA expression was significantly associated with clinical characteristics and survival outcomes in glioma patients.Conclusion KCNJ14 exhibits differential expression in glioma cells and is negatively associated with patient prognosis.Mechanistically,it may regulate glioma cell proliferation by modulating cell cycle related proteins.

Objective:To construct a clinical decision-making ability indicator system based on evidence-based practice for pediatric nursing interns, and to provide a scientific basis for clinical teaching and evaluation.Methods:A method combining literature analysis, Delphi expert consultation, and empirical research was used. Firstly, a systematic search of Chinese and English databases (2018-2023) was conducted. Literature was screened based on the PICO framework and evidence-based data were extracted, resulting in a preliminary system consisting of 4 primary indicators, 12 secondary indicators, and 39 tertiary indicators. Subsequently, the indicators were revised through two rounds of Delphi expert consultation (25 experts with 19-27 years of work experience). The expert authority coefficients (Cr) were 0.898-0.907 and the Kendall's concordance coefficients were 0.351-0.420 ( P<0.001). Finally, the analytic hierarchy process was used to determine the weights, and the reliability and validity were verified through a questionnaire survey (sample size: 30 participants in preliminary survey and 58 participants in formal survey). Results:The constructed indicator system included 4 primary indicators (weights), 13 secondary indicators, and 42 tertiary indicators. The weights of the primary indicators were as follows: knowledge integration ability (0.300), evidence-based practice ability (0.250), clinical judgment ability (0.280), and ethical decision-making ability (0.170). The importance scores of all items exceeded 4.0 points (out of 5 points), and the coefficients of variation were less than 0.20. The reliability and validity tests showed that the Cronbach's α of the overall scale was 0.89, and the intraclass correlation coefficient was 0.88. The cumulative variance contribution rate of exploratory factor analysis was 69.30%. The confirmatory factor analysis demonstrated a good model fit with a comparative fit index of 0.93 and a root mean square error of approximation of 0.05. Conclusions:This indicator system has high scientificity and practicality, and can provide a reference for the standardized cultivation and evaluation of clinical decision-making ability of pediatric nursing interns. In the future, it is necessary to strengthen advanced evidence-based skills training and long-term application effectiveness tracking.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.

Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.

Objective To investigate 5-aminoimidazole-4-carboxamide ribonucleotide formyl transferase/inosine monophos-phate cyclohydrolase(ATIC),a key regulator of metabolism and cell proliferation,to explore its role in glioma proliferation,e-valuate its association with patient prognosis,and elucidate the underlying molecular mechanisms.Methods Using data from The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx),and Chinese Glioma Genome Atlas(CGGA)databas-es,we analyzed differential ATIC expression between tumor tissues and adjacent normal tissues in glioma patients,as well as its correlation with clinical features including pathological grade,isocitrate dehydrogenase(IDH)mutation status,and chromosome 1p/19q deletion.ATIC was knocked down using siRNA transfection.The effect of ATIC on the proliferation of glioma cell lines(LN229,U373,and U251)was evaluated using EdU,CCK-8,and colony formation assays.Furthermore,ATIC overexpression via plasmid transfection was analyzed in conjunction with flow cytometry and Western blotting analysis to assess cell cycle pro-gression and cyclin-related protein expression.Results ATIC expression was significantly elevated in glioma tissues compared to adjacent normal tissues(P＜0.01).Patients with high ATIC expression exhibited shorter overall survival(OS)and were asso-ciated with higher pathological grades,wild-type IDH status,and the presence of chromosome 1p/19q deletion.Compared with U373 and U251 glioma cell lines,LN229 and U87 glioma cell lines demonstrated higher ATIC expression.In siRNA-mediated ATIC knockdown models(siATIC-LN229,siATIC-U373),cell proliferation was suppressed as demonstrated by EdU,CCK-8,and colony formation assays,whereas ATIC overexpression in U251 cells promoted proliferation.Flow cytometry revealed G1-phase arrest and impaired S-phase progression in siATIC-LN229 cells.Conversely,ATIC overexpression in U251 cells decreased G1-phase accumulation and increased S-phase progression.Mechanistically,ATIC knockdown decreased the expression of phos-phorylated Rb(p-Rb),upregulated p21,and downregulated key cyclin-related proteins essential for G1/S transition.In contrast,ATIC overexpression facilitated the G1/S transition through p21 downregulation and enhanced phosphorylation of Rb pro-tein.Conclusion High ATIC expression is associated with poor clinical outcomes in glioma patients and may promote tumor progression through regulation of the p21-Rb signaling pathway.Therefore,ATIC represents a promising biomarker for both clinical diagnosis and prognosis in glioma.