[The prognostic evaluation of coronary artery calcification score and CT fractional flow reserve for patients with stable coronary artery disease].

Objective: To investigate the prognostic value of coronary artery calcium score (CACS) and computed tomography-derived fractional flow reserve (CT-FFR) for major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD). Methods: The data for this prospective study were derived from a prospective clinical trial at a single center. This trial enrolled stable CAD patients who underwent coronary CT angiography (CCTA) in General Hospital of Eastern Theater Command from April 2018 to March 2019 and had coronary artery stenosis of 25%-80%. Patients were assigned to either the control group or trial group according to CCTA time. Patients in control group were provided with only a standard CCTA report, while patients in trial group were provided with both a standard CCTA report and the corresponding CT-FFR results. The study included patients who underwent ECG-gated calcium scoring CT scans in this trial. CT-FFR value at 2 cm distal to the narrowest stenosis of each vessel was calculated. The minimum CT-FFR value was recorded as the patient level and CT-FFR≤0.80 was defined as a positive result. All patients were followed up for MACE, including all-cause death, nonfatal myocardial infarction, and acute coronary syndrome leading to unplanned revascularization. Multivariable Cox proportional hazards regression analysis was used to identify variables associated with MACE occurrence, and the Concordance index (C-index) was used to represent the performance of the models for predicting MACE occurrence based on clinical, anatomical, and CT-FFR parameters. Results: A total of 783 patients were finally statistically analyzed, with a age of (62.0±10.8) years, of whom 64.6% (506 cases) were male. There were 383 patients in the trial group and 400 patients in the control group, with a median follow-up time of 35.3 months. A total of 81 MACE cases occurred during the follow-up. The incidence of MACE in trial group (8.1%, 31/383) was significantly lower than that in control group (12.5%, 50/400)(χ2=4.095, P=0.043). CACS≥300, stenosis≥70% and CT-FFR≤0.80 [HR (95%CI) were 2.14 (1.01-4.52), 5.38 (3.44-8.42) and 16.91 (9.21-31.04), all P<0.05] showed predictive value for MACE. The predictive ability of the CT-FFR model is significantly better than that of the CACS model and the stenosis degree model [C-index (95%CI) were 0.850 (0.823-0.874), 0.653 (0.618-0.686) and 0.718 (0.685-0.749), all P≤0.001]. The comprehensive model with added CACS and stenosis degree did not significantly improve the predictive value of the CT-FFR model [C-index (95%CI) were 0.867 (0.841-0.890), 0.850 (0.823-0.874), P=0.584]. Conclusions: CT-FFR has a high predictive value for MACE in patients with stable CAD, the combination of CT-FFR and CACS did not increase the predictive power of CT-FFR.

[Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway].

OBJECTIVE: To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS). METHODS: Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low, moderate and high doses (50, 100 and 200 mg/kg, respectively, n=8), VX765 (a caspase-1 specific inhibitor, 50 mg/kg, n=8), or fluoxetine (10 mg/kg, n=8) on a daily basis for 4 weeks, and the changes in depression-like behaviors of the mice were assessed by sugar water preference test, forced swimming test and tail suspension test. The expression of glial fibrillary acidic protein (GFAP) in the hippocampus of the mice was detected using immunohistochemistry, and the number of synaptic spines was determined with Golgi staining. Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus, and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay. RESULTS: Compared with the normal control mice, the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests (P < 0.05), and these depression-like behaviors were obviously improved by treatment with coenzyme Q10, VX765 or FLX. The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines, enhanced expressions of GSDMD-N, caspase-1 and IL-1ß, and increased colocalization of neurons and caspase-1 p10 (all P < 0.05). All these changes were significantly ameliorated in the mouse models after treatment with Q10. CONCLUSION: Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Retraction Note: LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression.

The article "LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression", by R.-F. Zhang, J.-W. Liu, S.-P. Yu, D. Sun, X.-H. Wang, J.-S. Fu, Z. Xie, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6774-6782-DOI: 10.26355/eurrev_201908_18715-PMID: 31486475 has been retracted by the authors for the following reasons: - The data presented in the manuscript require further validation, which may affect the results. After careful consideration, we have decided to withdraw it to ensure its reliability and reproducibility. All authors concur with this decision. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18715.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

[Incidence of common gene mutations in early-onset colorectal cancer and the association with cancer survival: a meta-analysis].

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Biocontrol of strawberry Botrytis gray mold and prolong the fruit shelf-life by fumigant Trichoderma spp.

Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.

A high resolution reaction microscope with universal two-region time-focusing method.

This paper presents a novel reaction microscope designed for ion-atom collision investigations, established at the Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China. Its time-of-flight (TOF) spectrometer employs an innovative flight-time focusing method consisting of two acceleration regions, providing optimal time focusing conditions for charged fragments with diverse initial velocities. The TOF spectrometer's axis intentionally tilts by 12° relative to the ion beam direction, preventing potential obstructions from the TOF grid electrodes. The introduced focusing method allows for a flexible time-focusing TOF spectrometer design without restricting the length ratio of the two regions. In addition, this configuration in our case significantly suppresses noise on the recoil ion detector produced by residual gas in the ion beam trajectory, which is a considerable challenge in longitudinal spectrometers. In a test experiment on the single electron capture reaction involving 62.5 keV/u He2+ ions and a helium atomic beam, the recoil longitudinal momentum resolution achieved 0.068 atomic units. This novel configuration and successful test run show excellent precision for ion-atom collision studies.

Antioxidant effect of dimethyl fumarate in pentylenetetrazole-kindled epilepsy mice and is activated by nuclear factor erythroid 2-related factor 2 pathway.

This study was designed to examine the anti-oxidative stress effect of dimethyl fumarate (DMF) on pentylenetetrazole (PTZ)-induced epileptic mice, and to evaluate the correlation of its mechanism with the nuclear factor E2-related factor 2 (Nrf2)-mediated signaling pathway. The experimental mice were separated into three groups: control, model, and DMF groups. Mice in the model group were administered PTZ to establish an epilepsy model, mice in the DMF group were administered DMF concurrently when modeling, and mice in the control group were administered a 0.9% NaCl solution. The latency, severity, and frequency of epileptic seizures in mice after each treatment were recorded, and the modelling success rate was computed at the conclusion of the experiment. The mice were euthanized, their levels of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), 8-hydroxy-deoxyguanosine (8-OHdG), and Nrf2 were measured, and the electron microscope was used to examine the mitochondrial damage of brain tissue. The latency of epileptic seizures was longer in the DMF group compared to the model group (P<0.05). The levels of MDA and ROS in the DMF group were lower than those in the model group (P<0.0001), and the activity of SOD in the DMF group was higher than that in the model group (P<0.0001); however, the levels of MDA and ROS were elevated and the activity of SOD was lower in both groups relative to the control group. The levels of 8-OHdG were lower in the DMF group than the model group (P<0.0001), however, the levels were higher in both groups compared to the control group. Mitochondrial abnormalities were more prevalent in the model group than in the DMF group, and more prevalent in both groups compared to the control group. The DMF group contained more Nrf2 content than the model group (P<0.0001), and both groups contained more Nrf2 than the control group. We concluded that the mechanism by which DMF reduced the level of oxidative stress in epileptic mice might involve the Nrf2-mediated signaling pathway.

[Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection].

OBJECTIVE: To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. METHODS: Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson's trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. RESULTS: Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson's trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/µm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/µm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). CONCLUSIONS: E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

[L-DEP regimen salvage therapy for refractory primary hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection in 4 children].

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Study on the construction of nomogram prediction model for prognostic assessment of heart failure patients based on serological markers and echocardiography.

OBJECTIVE: We aimed to construct a nomogram prediction model for prognostic assessment of patients with heart failure (HF) based on serological markers and echocardiography. PATIENTS AND METHODS: A total of 200 HF patients admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to January 2020 were selected as the research objects. According to the New York Heart Association (NYHA) cardiac function classification, they were divided into 3 groups, including 65 cases of grade II, 97 cases of grade III, and 38 cases of grade IV. Three groups of echocardiographic parameters were compared [including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], differences in serum markers brain natriuretic peptide (BNP), soluble growth-stimulating expression gene 2 (sST2) and the Modified Early Warning Score (MEWS). The patients were divided into two groups according to their clinical outcomes during the follow-up period, including 52 cases in the death group and 148 cases in the survival group. The clinical data of the two groups were compared, and multi-factor logistic regression analysis was performed to screen out the independent risk factors affecting the patient's death. A nomogram model of the patient's mortality risk was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the discrimination and accuracy of the nomogram model. RESULTS: As the cardiac function class of elderly chronic heart failure (CHF) patients increases, LVEDD, LVESD, sST2, and MEWS increase and LVEF decreases (p<0.05). Multifactor analysis results showed that LVEF, LVEDD, sST2, and MEWS were independent factors affecting the clinical outcome of patients. The AUCs predicted using LVEF, LVEDD, sST2, and MEWS alone were 0.738, 0.775, 0.717, 0.831, and 0.768, respectively. There is a certain degree of discrimination, and the model has extremely high accuracy. CONCLUSIONS: MEWS, LVEDD, and sST2 increase as the NYHA cardiac function grade of HF patients increases and LVEF decreases, which can reflect the severity of the disease to a certain extent. Additionally, the nomogram model established based on this has a high predictive value for the long-term prognosis of patients and can formulate effective intervention measures for quantitative values.

Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.

Objective: The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). Methods: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model. Results: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias. Conclusion: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.

[Genetic characteristics and clinical analysis of 20 patients with Gaucher's disease].

Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder characterized by high heterogeneity. This study aimed to further understand the correlation between clinical phenotypes and genotypes in GD patients through a retrospective analysis of 20 cases in Shanxi Bethune Hospital, including their clinical manifestations, laboratory tests, enzyme studies, and genetic results. Among the 20 GD patients, 16 were classified as Type Ⅰ GD with a median age of diagnosis of 24 years, and 4 were classified as Type Ⅲ GD with a median age of diagnosis of 19 years. All patients exhibited splenomegaly and thrombocytopenia, with 16 patients showing skeletal imaging changes, and 5 of them presenting with bone pain symptoms. Genetic analysis revealed 15 distinct mutations, predominantly missense mutations, with L483P being the most prevalent (35.7%), followed by V414L, L303I, and F252I. Mutation sites were predominantly located in exon 7. Noteworthy findings included the first report of the S310G mutation by our research group and the first occurrence of the K196R mutation in the Chinese population. Additionally, the N227S mutation was implicated in a potential association with neuropathy. Despite advancements, Uncertainties still exist in the correlation between clinical phenotypes and genotypes in GD patients.

[Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil].

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

[Standardization of next-generation sequencing for detecting mutations associated with targeted therapy and immunotherapy based on dynamic pattern of expandable detection range].

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.

Factors influencing the willingness to pay a price premium for red meat with potential to improve consumer wellness in Australia and the United States of America.

This study determined consumers' attitudes towards physical and mental wellness related to red meat consumption and their willingness to pay (WTP) more for the meat. In 2019, two online surveys of red meat eaters were conducted in the USA (n = 1000) and Australia (n = 523) using commercial platforms. Results showed that over 90% of respondents indicated interest in purchasing red meat to improve their wellness status. Additionally, about 85% indicated their WTP more for red meat for its wellness benefits, with Americans indicating stronger willingness than Australian respondents. The potential of meat consumption to improve overall wellness among red meat eaters was a dominant factor influencing consumers' WTP more. Other factors that increased WTP included frequency of meat consumption, physical exercise, sleep quality, number of children in a household, partnership status, and economic position. Outcomes from this study highlight a unique opportunity for the meat industry to position meat on its qualities that include wellness improvement if backed up with robust scientific evidence.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study.

AIMS: To evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). METHODS: A retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. RESULTS: Yolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I-II and stages III-IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1-2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). CONCLUSION: Distinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

[The therapeutic effect and prognostic value of oligoclonal bands after autologous stem cell transplant in patients with multiple myeloma].

Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.