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*

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.

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.

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.

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.

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.

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:To explore the relationship between lipid accumulation product (LAP) and disease activity, nutritional status in patients with Crohn disease (CD).Methods:The clinical data of 74 patients with CD in the Affiliated Hospital of Yangzhou University from July 2020 to June 2021 were retrospectively analyzed. The patients were divided into active group (32 cases) and remission group (42 cases) according to simplified Crohn disease activity index (CDAI). The general clinical data, laboratory examination results and body fat indexes were recorded, body fat indexes including body mass index (BMI), waist circumference, waist-to-height ratio, LAP and nutritional risk screening 2002 (NRS2002) score. Spearman method was used for correlation analysis; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of LAP in predicting the disease activity and nutritional status in patients with CD.Results:The proportion of males, body weight, hemoglobin, albumin, total cholesterol, triglyceride and high-density lipoprotein cholesterol in active group were significantly lower than those in remission group: 46.9% (15/32) vs. 71.4% (30/42), (53.58 ± 8.13) kg vs. (61.05 ± 9.38) kg, (109.94 ± 23.70) g/L vs. (134.19 ± 18.03) g/L, (34.01 ± 5.71) g/L vs. (39.15 ± 4.27) g/L, (3.23 ± 0.68) mmol/L vs. (3.66 ± 0.74) mmol/L, (1.12 ± 0.36) mmol/L vs. (1.34 ± 0.55) mmol/L and (0.91 ± 0.23) mmol/L vs. (1.04 ± 0.33) mmol/L, the nutritional risk rate, platelet count, C-reactive protein and erythrocyte sedimentation rate were significantly higher than those in remission group: 68.8% (22/32) vs. 19.0% (8/42), (317.97 ± 130.19) ×10 9/L vs. (194.00 ± 51.91) × 10 9/L, 14.15 (6.15, 41.35) mg/L vs. 1.51 (0.22, 5.58) mg/L and 40.00 (20.50, 64.25) mm/1 h vs. 9.00 (3.00, 20.00) mm/1 h, and there were statistical differences ( P<0.01 or <0.05); there were no statistical difference in age, height, total protein and low-density lipoprotein cholesterol between the two groups ( P>0.05). The BMI, waist circumference, waist-to-height ratio and LAP in active group were significantly lower than those in remission group: 19.46 (17.70, 21.45) kg/m 2 vs. 21.08 (18.87, 23.12) kg/m 2, (72.51 ± 5.92) cm vs. (77.67 ± 7.27) cm, 0.44 ± 0.03 vs. 0.46 ± 0.04, 13.42 (5.07, 17.72) cm·mmol/L vs. 15.49 (9.37, 31.71) cm·mmol/L, the NRS2002 was significantly higher than that in remission group: 3.00 (1.00, 3.75) scores vs. 1.00 (0, 2.00) scores, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that LAP was positively correlated with BMI, waist circumference and waist-to-height ratio ( r = 0.701, 0.766 and 0.829; P<0.01); LAP was negatively correlated with NRS2002 score, platelet count and erythrocyte sedimentation rate ( r =- 0.609, - 0.249 and - 0.243; P<0.01 or<0.05). ROC curve analysis result showed that the areas under the curve of LAP predicting disease remission and nutritional status improvement in patients with CD were 0.645 and 0.832 (95% CI 0.520 to 0.770 and 0.739 to 0.925), the best cut-off values were 20.89 and 12.86 cm·mmol/L, the sensitivities were 45.2% and 81.8%, and the specificities were 87.5% and 73.3%. Conclusions:LAP has good predictive value for disease remission and nutritional status improvement in patients with CD.

The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.