Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Objective:To explore the impact of transcranial direct current stimulation (tDCS) on ischemic stroke survivors in terms of its association with neurotrophic factors in a person′s peripheral blood.Methods:Forty ischemic stroke survivors were randomly allocated into a control group and a treatment group, each of 20. Both groups were given routine medication and rehabilitation, while the treatment group was additionally provided with 20 minutes of tDCS daily at an intensity of 2.0mA. There were 14 sessions over two weeks. The control group received sham stimulation. Before and after the experiment, both groups were assessed using the Modified Barthel Index (MBI), the Mini-mental State Examination (MMSE), the Hamilton Depression Scale (HAMD), and the Self-rated Depression Scale (SDS). The concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the subjects′ peripheral blood were quantified using enzyme-linked immunosorbent assays (ELISAs).Results:Baseline comparisons revealed no significant disparities between the two groups in their average MBI, MMSE, HAMD, or SDS results, nor in their average BDNF or NGF levels. Post-treatment assessments indicated significant enhancements across these metrics within both groups. Notably, the treatment group then exhibited average MBI and MMSE scores superior to those of the control group, alongside a lower average HAMD score. Furthermore, elevated levels of BDNF [(108.20±36.96)pg/ml] and NGF [(2.90±1.03)pg/ml] were observed in the treatment group.Conclusion:tDCS appears to significantly enhance cognition, minimize symptoms of depression, and augment self-care ability after an ischemic stroke. These benefits are possibly mediated through the increase of neurotrophic factor levels.

Objective: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. Methods: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. Results: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. Conclusion DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Objective: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. Methods: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. Results: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. Conclusion DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Objective: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. Methods: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. Results: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. Conclusion DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. Methods: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. Results: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. Conclusion DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Objective: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. Methods: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. Results: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. Conclusion DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Objective:To investigate the effect of quality improvement (QI) project on delayed cord clamping (DCC) implementation in very preterm infants.Methods:This study retrospectively collected the clinical data and assessed the QI indices of very preterm infants born in the Women and Children's Hospital of Chongqing Medical University and transferred to the Neonatology Department from January 2017 to January 2021. The indices for QI assessment included three types: (1) process indices: the implementation rate and timing of DCC; (2) outcome indices: hemoglobin level and hematocrit, etc; (3) balancing indices: the proportion of neonates requiring endotracheal intubation in the delivery room and chest compressions, Apgar score body temperature, and blood pH value on admission, etc. There were four phases for the implementation of QI, the pre-QI period (January to December of 2017), the QI period (January to December of 2018), the post-QI period (January to December of 2019), and the sustained-QI period (January 2020 to January 2021). The QI project was performed since August 2018. Control charts or statistical tests were used for statistical analysis.Results:(1) Process indices: After the implementation of the QI project, the practice of DCC increased from 0 to 82.2%, and the timing of umbilical cord clamping was from 0 s to a delay of 47.1 s. (2) Outcome indices: The levels of hemoglobin in the QI period, the post-QI period, and the sustained-QI period were significantly higher than those in the pre-QI period [(202.22±28.84), (210.10±33.52), (210.52±32.27) g/L vs. (187.94±35.29) g/L; F=8.61, P<0.001]. The hematocrit values in the post-QI period and the sustained-QI period were significantly higher than those in the pre-QI period [(58.99±8.71) %, (60.18±8.06)% vs. (55.41±9.17)%; χ2=5.13, P=0.002]. The other indices showed no statistical differences in different phases. (3) Balancing indices: The proportions of neonates receiving endotracheal intubation in the delivery room in the post-QI period and the sustained-QI period were significantly lower than those in the pre-QI period [16.0% (19/119), 13.2% (25/191) vs. 42.3% (30/71); χ2=29.08, P<0.001]. The body temperature on admission increased gradually through the four periods [pre-QI period: 35.3 ℃ (34.5-36.1 ℃); QI period: 36.0 ℃ (34.0-37.7 ℃); post-QI period: 36.0 ℃ (35.6-37.4 ℃); sustained-QI period: 37.0 ℃ (35.9-38.1 ℃); H=277.88, P<0.001]. The blood pH value on admission in the sustained-QI period [7.32 (6.85-7.50)] was significantly higher than those in the other three periods [7.26 (7.07-7.46), 7.26 (7.04-7.43), and 7.25 (6.91-7.49); H=34.46, P<0.001]. Conclusion:The interventions in this QI project significantly increase the practice of DCC and enable a longer DCC in very preterm infants.

Background: Stroke is one of the leading causes of death around the world. The sequelae of ischemic stroke cause drastic effects on the quality of life for patients. Sanwujiaowan (SWJW) is a mixture prepared with 5 herbal medicines (Aconiti Lateralis Radix Praeparata, Aconiti Kusnezoffii Radix, Polygoni Multiflori Radix, Aconiti Radix, and Olibanum), with a long history of application in treating the sequelae of stroke. Objectives: To provide evidence and decipher the mechanism of SWJW in alleviating stroke. Materials and methods: In this article, we expanded the indicators of SWJW by an integrated strategy based on signature metabolomics, target proteins, and bioinformatics and probed into the mechanism of SWJW intervention in ischemic stroke in a rat model. Results: The results indicated that SWJW protected rats from nerve damage during the acute phase of ischemic stroke by regulating tau phosphorylation via the PI3K/Akt pathway. Conclusions: This study, for the first time, proved that the reduction of phosphorylated tau was harmful for the neural function in the acute phase of ischemic stroke. Meanwhile, the pathological changes of phosphorylated tau proteins were detected in stroke and recalled by SWJW. This finding may provide a new reference for formulating treatment strategies for the acute phase of ischemic stroke.