ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Alzheimer's disease （AD） is a neurodegenerative disease that leads to progressive memory and cognitive impairment and behavioral disorders， which has seriously threatened the health of the majority of middle-aged and elderly people. Traditional Chinese medicine （TCM） believes that the basic pathogenesis of AD is deficiency of kidney-essence， blood stasis and meridian stagnation. In recent years， many studies have shown that TCM has obvious value and advantages in the prevention and treatment of AD by multi-target mechanism. Therefore， it is of great significance to screen out effective anti-AD drugs from TCM compound prescriptions. Huangjingwan， also known as Jiuzhuan Huangjingwan， has the effects in tonifying kidney-essence， activating blood and removing stasis， with a potential effect in preventing AD. In this article， the feasibility of Huangjingwan in the prevention and treatment of AD was analyzed and discussed from the perspective of TCM theory， the study results of Huangjingwan in the prevention and treatment of AD were summarized， and the mechanism of its action was analyzed from the perspective of pharmacological mechanism. Based on TCM theory， Huangjingwan has the effect of anti-AD. According to relevant findings， Huangjingwan has many targets， such as anti-oxidation， anti-inflammatory， decrease of the level of oxidative stress in brain， activation of Wnt/β-catenin signal transduction in brain， regulation of glycogen synthase kinase-3β （GSK-3β）， protein phosphatase 2A （PP2A） activity balance， reduction of amyloid β （Aβ） content and tau protein hyperphosphorylation in brain， so as to exert effects in improving neurological symptoms and increasing learning and memory ability， with an anti-AD neuroprotective function. This will provide new ideas for in-depth studies and clinical applications of Huangjingwan against AD.

OBJECTIVE: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS). METHODS: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared. RESULTS: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ=7.180, P=0.007) and (20.0% vs 6.7%) ( χ=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ=16.653, P=0.000) and (23.6% vs 8.7%)(χ=9.041, P=0.003) respectively. CONCLUSION The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

OBJECTIVE: To investigate the effect of baicalin derivative 02-036 on proliferation and apoptosis human Burkitt lymphoma cell line CA46 and its related mechanisms. METHODS: The MTT assay and cell colony formation assay were used to measure the growth inhibition of CA46 cells after 02-036 treatment. The flow cytometry with AnnexinV-FITC/PI double staining was employed to detect the apoptosis induction effect of 02-036 on CA46 cells. Cell cycle distribution of CA46 cells was estimeted by using DNA ploid analysis. Western blot was used to determine the changes of apoptosis-related proteins, including C-MYC, BCL-2, Procaspase-9, Procaspase-3, PARP and Cleaved-PARP. RESULTS: Baicalin derivative 02-036 obviously inhibited the proliferation of CA46 cells, with dose- and time-dependent manner (r=0.963, r=0.992). The averaged IC value of CA46 cells was (6.04±0.11) μmol/L after 48-hour treatment. Low concentration of 02-036 could significantly inhibit the colony formation of CA46 cells. Flow cytometry analysis confirmed that 02-036 could effectively induce CA46 cell apoptosis. The apoptosis rate correlated with drug concentrations (r=0.959). Also, DNA ploid analysis showed that the cell cycle of CA46 was arrested in the S phase. The expression levels of BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC proteins decreased with a 02-036-dose dependent manner (r values were -0.990, -0.939, -0.971 and -0.967, respectively). In contrast, the expression level of cleaved-PARP increased with the same manner (r=0.920). CONCLUSION Baicalin derivative 02-036 can effectively inhibit the proliferation and induce apoptosis of CA46 cells, and its related mechanisms may be correlated with the down-regulation of apoptosis-related molecule expression levels, such as BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC.
Apoptosis ; Burkitt Lymphoma ; Cell Line, Tumor ; Cell Proliferation ; Flavonoids ; Humans

Loureirin A is a major active component of Draconis sanguis, a traditional Chinese medicine. This work aimed to investigate the activity of loureirin A against Candida albicans biofilms. 2, 3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)reduction assay and scanning electron microscopy were used to investigate the anti-biofilm effect. Minimal inhibitory concentration testing and time-kill curve assay were used to evaluate fungicidal activity. Cell surface hydrophobicity (CSH) assay and hyphal formation experiment were respectively carried out to investigate adhesion and morphological transition, two virulence traits of C. albicans. Real-time RT-PCR was used to investigate gene expression. Galleria mellonella-C. albicans and Caenorhabditis elegans-C. albicans infection models were used to evaluate the in-vivo antifungal effect. Human umbilical vein endothelial cells and C. elegans nematodes were used to evaluate the toxicity ofloureirin A. Our data indicated that loureirin A had a significant effect on inhibiting C. albicans biofilms, decreasing CSH, and suppressing hyphal formation. Consistently, loureirin A down-regulated the expression of some adhesion-related genes and hypha/biofilm-related genes. Moreover, loureirin A prolonged the survival of Galleria mellonella and Caenorhabditis elegans in C. albicans infection models and exhibited low toxicity. Collectively, loureirin A inhibits fungal biofilms, and this effect may be associated with the suppression of pathogenic traits, adhesion and hyphal formation.

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.
Animals ; Disease Models, Animal ; Fluorescein Angiography ; Hemodynamics ; physiology ; Humans ; Male ; Optic Disk ; pathology ; physiopathology ; Optic Neuropathy, Ischemic ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells ; physiology

OBJECTIVETo investigate the expression of CC-chemokine receptor 7(CCR7) in patients with multiple myeloma(MM) and its correlation with clinical features of MM.

METHODSThe level of CCR7 expression in bone marrow samples from 53 newly diagnosed MM patients was detected by flow cytometry(FCM). Statistical methods were used to analyze the correlation between CCR7 expression and clinical features, such as sex, age, M protein, peripheral blood cell count, biochemical indicators, plasma cell ratio of bone marrow, immunophenotype, osteopathy and extramedullary disease.

RESULTSThe plasma cells in 24 out of 53 cases(45.28%) expressed CCR7. The rate of extramedullary disease in CCR7 positive group was significantly higher than that in CCR7 negative group (29.17% vs 3.45%)(P<0.05).

CONCLUSIONThe expression of CCR7 in patients with MM is high, moreover this high expression correlates with extramedullary disease, thus CCR7 can be used as an effective indicator for prediction of extramedullary disease.