BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

This article explores the MRI-guided proton therapy(MRiPT)integrated technology,which is magnetic resonance imaging-guided radiation therapy.By precisely controlling dose distribution,MRiPT has the potential to enhance the efficacy of radiotherapy.This article reviews the development of MRiPT,analyzes its potential for clinical application,and discusses technical challenges and potential solutions.MRiPT technology offers significant advantages in improving treatment precision and reducing side effects,especially showing exceptional potential in the treatment of complex tumors.This article concludes by looking forward to the future development of MRiPT technology,emphasizes the importance of optimizing electromagnetic compatibility and reducing inter-system interference.

ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription （YHP） on the learning and memory of accelerated aging model mice， as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups， including the model group， low-dose YHP group， high-dose YHP group， and donepezil group. Additionally， 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group， each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg^-1 and 12.48 g·kg^-1， while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg^-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial （MG） polarization marker inducible nitric oxide synthase （iNOS） and M2 MG polarization marker arginase-1 （Arg-1） in the hippocampus region. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of pro-inflammatory factor interleukin 1β （IL-1β） and anti-inflammatory factor transforming growth factor-β₁ （TGF-β₁）. Furthermore， Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 （Aβ_1-42） along with triggering receptor expressed on myeloid cells 2 （TREM2）/nuclear factor kappa B （NF-κB） signaling pathway-related proteins TREM2， phospho （p）-NF-κB p65， and phospho-inhibitory kappa B kinase β （IKKβ） in the hippocampus. ResultCompared with the control group， the model group exhibited a significantly prolonged escape latency （P<0.01）， a significant reduction in neuron-specific nuclear protein （NeuN） expression in the hippocampus， a significant increase in iNOS expression in MG， and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased， while the TGF-β₁ content was significantly decreased. Additionally， there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions （P<0.05， P<0.01）. However， no significant changes were observed in escape latency， times of crossing the platform， and hippocampal NeuN expression in the YHP treatment control group. Conversely， iNOS expression in MG as well as the hippocampal p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions were significantly decreased. Furthermore， TREM2 expression was significantly increased （P<0.05， P<0.01）. In comparison to the model group， the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform （P<0.05， P<0.01）. In the high-dose YHP group， the escape latency was significantly shortened （P<0.05）. In the low-dose YHP group， high-dose YHP group， the expression of NeuN in the hippocampus was significantly increased， the expression of iNOS in MG was significantly decreased， and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased， while the TGF-β₁ content was significantly increased. Furthermore， the expression of TREM2 in the hippocampus was significantly increased， and the expressions of p-NF-κB p65， p-IKKβ， and Aβ_1-42 were significantly decreased （P<0.01）. ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway， reduce the release of neuroinflammatory factors， protect hippocampal neurons， and reduce the deposition of Aβ_1-42， and finally delay the occurrence of learning and memory decline in SAMP8 mice.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Background/Aims: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. Methods: Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. Results: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. Conclusions Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

To revise GBZ 188 Technical Specification for Occupational Health Surveillance based on national laws, regulations, standards, specifications and legal documents of occupational disease, and combination with the actual situation in China. The main modifications are as follows: the occupational health surveillance for workers exposed to toluene (xylene may implement by reference), bromopropane, methyl iodide, ethylene oxide, chloroacetic acid, indium and its compounds, coal tar, coal tarasphalt, asphalt, β-naphthylamine, dust of metal and its compounds(tin, iron, antimony, barium and its compounds), hard metal dust, erionite dust, low temperature, laser, tick-borne encephalitis virus, Borrelia burgdorferi, and human immunodeficiency virus, for scraper or grind operators, and underground workers using squatting or kneeling position, crawling position, side-lying position, or shoulder position for a long period of time are included. The emergency health screening for workers exposed to arsenic, fluorine and its inorganic compounds, and acrylamide are included. The occupational medical examination (OME) for workers exposed to amino and nitro compounds of benzene, phosgene, monomethylamine, organic fluorine and dimethyl sulfate has been adjusted and made mandatory, with corresponding assessments required upon leaving the job. The special occupational health surveillance for workers exposed to mycobacterium tuberculosis and hepatitis virus is removed. The OME conclusion of reexamination is removed, and standardize recheck/additional inspection requirements. The optional items in OME performed before, during and after leaving post are removed, but the optional items in emergency medical examination are retained. Additional OME items are added. The Guideline for OME Summary Reports is added as informative appendix, and so on. The revised GBZ 188 Technical Specification for Occupational Health Surveillance is more scientific and practical.

Objective To explore the potential mechanism of"hot flashes"in mice with type 2 diabetes with yin deficiency syndrome.Methods Ninety-nine 8-week-old db/db mice with fasting blood glucose≥16.7 mmol·L-1 were divided into yin deficiency syndrome group,type 2 diabetes group,type 2 diabetes with yin deficiency syndrome group,type 2 diabetes with Liuwei Dihuang Decoction low,medium,high-dose group,type 2 diabetes with yin-deficiency syndrome and Liuwei Dihuang Decoction low,middle,high-dose groups,21 littermates of wild control male m/m mice were control group.The model was established by the method of"heat engenders yin deficiency",and the performance of yin deficiency syndrome in mice was evaluated after 4 weeks.Afterwards,the corresponding doses of Liuwei Dihuang Decoction group were given by gavage for 4 weeks.During the experiment,the rectal temperature,the temperature of the precordial area,and the temperature of the limbs and paws were measured once a week at 8:30,15:00,and 20:00.Western blot was used to observe the expression of biological rhythm-related proteins in the hypothalamus and liver.Results The experimental study showed that the yin deficiency syndrome model of type 2 diabetes could be established by using the method of overheating and injuring the yin.The rhythm changes of Liuwei Dihuang Decoction showed that the high-dose group could effectively restore the body temperature rhythm.The expression of rhythm factors Clock and Cry2 increased in both the hypothalamus and liver;in the hypothalamus,the central rhythm regulation center,the expressions of Per2 and Cry2 increased significantly;in the peripheral target organ liver,the expressions of Bmal1,Per3 and Cry1 increased more significantly.Conclusion The abnormal expression of biological rhythm protein in the liver and hypothalamus may be one of the important mechanisms leading to the characteristics of"hot flashes"in type 2 diabetes with yin deficiency.

Objective:Rapid assessment of the outcome after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is an important clinical issue. In this study, an electrocardiogram (ECG) analysis method based on dynamic learning was proposed.Methods:A total of 203 patients with ACS after successful PCI were enrolled for prospective analysis at the Emergency Department of Qilu Hospital of Shandong University from April 2019 to December 2020. All patients were divided into group without ≥70% postoperative stenosis ( n=72) and group with ≥ 70% postoperative stenosis ( n=131) according to the presence of 70% or more stenosis after PCI. The clinical data of ACS patients were collected and analyzed by χ2 test, t-test, or Mann-Whitney test. ECGs were recorded before and 2 h after PCI, and were dynamically analyzed to generate cardiodynamicsgram (CDG) using dynamic learning. In the group without ≥ 70% postoperative stenosis, the model and CDG index for evaluating myocardial ischemia were obtained by training support vector machine (SVM) using 10 times 10-fold cross-validation. Results:There was no significant difference in clinical data between the two groups. The prediction accuracy and sensitivity of the support vector machine model for myocardial ischemia in group without≥70% postoperative stenosis were 73.61%, and 84.72% respectively. CDG transformed from disorderly to regular after PCI, and CDG index decreased significantly ( P<0.001): 90.28% (65) patients in group without≥70% postoperative stenosis, and 79.39% (104) patients in group with≥70% postoperative stenosis had lower CDG indexes than before PCI. Conclusions:In this study, CDG obtained by dynamic learning can intuitively and effectively evaluate the changes of myocardial ischemia before and after PCI, which is helpful to assist clinicians to formulate the next treatment plan.

Objective:To investigate the clinical epidemiological data of children with prolonged mechanical ventilation (PMV) in pediatric intensive care unit(PICU), and analyze the primary disease of children with PMV as well as the disease characteristics and prognosis of children with PMV under different kinds of primary disease.Methods:The clinical data of hospitalized children with PMV in PICU at Children′s Hospital of Fudan University from January 2019 to December 2020 were retrospectively collected.Results:A total of 46 children with PMV were collected.There were 18 males (39.1%) and 28 females (60.9%). The median age was 37 (8, 86) months and the median body weight was 15 (7, 20) kg.The average pediatric critical illness score at admission was 84.2±7.7, PaO 2/FiO 2 was (245.5±99.8)mmHg.The primary diseases leading to PMV were as follows: there were 14 cases of severe pneumonia, eight cases of severe encephalitis, five cases of bronchopulmonary dysplasia, three cases of upper airway obstruction/craniofacial deformity, three cases of myasthenia, three cases of brain stem tumor, three cases of mitochondrial encephalomyopathy, two cases of spinal muscular atrophy, two cases of Prader-Willi syndrome, one case of dermatomyositis, one case of severe brain injury, and one case of central hypoventilation.The causes of unable to withdraw ventilator were respiratory dysfunction in 24 cases, brain dysfunction in 16 cases, and diaphragm dysfunction in six cases.Compared with neuromuscular diseases, children with PMV caused by respiratory diseases had lower month age, higher preterm birth rate, lower PaO 2/FiO 2 ratio, higher parameters for ventilator treatment, and the differences were statistically significant ( P<0.05). Children with PMV caused by neuromuscular diseases had lower Glasgow coma score and higher coma rate, and the differences were statistically significant ( P<0.05). A total of nine (19.6%) cases underwent tracheotomy.A total of 23 (50.0%) cases were successfully extubated from ventilator, six (13.0%) cases were dependent on invasive ventilator, and six (13.0%) cases were breathing with tracheotomy tube.The median mechanical ventilation time was 33 (28, 40) days, the median PICU hospital stay was 42 (34, 56) days, and the median hospital stay was 51 (41, 65) days.A total of 27 (58.7%) cases were improved and discharged, four (8.7%) cases were transferred to rehabilitation hospital, four (8.7%) cases were transferred to local hospital, and 11 (23.9%) cases died in hospital or at home after giving up. Conclusion:The main causes of PMV in PICU children are respiratory dysfunction, brain dysfunction and diaphragm dysfunction.50.0% of the children with PMV could be discharged from the ventilator, and 23.9% died or died after giving up.