Objective To evaluate the methodological quality and measurement attribute quality of the evaluation tool for pediatric palliative care quality assessment tools,and to provide references for medical staff to select the best assessment tools.Methods The PubMed,Embase,Cochrane Library,Web of Science,CINAHL,Scopus,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database,Chinese Biomedical Literature Database,GIN,NGC,NICE,NRAO,medlive,WHO,AAHPM,WHPCA,APHN were searched from inception to March 28,2024.Data were screened and extracted independently by 2 researchers.The consensus-based standards for the selection of health measurement instruments(COSMIN)checklist and quality criteria were employed to evaluate the methodological quality and psychometric properties of the included pediatric palliative care quality assessment tools.Finally,recommendations were formulated based on these evaluations.Results A total of 13 articles were included,involving 9 pediatric palliative care quality assessment tools.Among them,the PICU-QODD,PaPEQu and QCPCI demonstrated good content validity and internal consistency,and are recommended as Grade A.The remaining assessment tools are recommended as Grade B or C.Conclusion The PICU-QODD,PaPEQu and QCPCI are recommended for use,but further validation of their psychometric properties is still needed.

Objective To systematically review the application and effectiveness of deep learning(DL)in diagnosis of mild cogni-tive impairment(MCI)among older adults.Methods PubMed,Web of Science,CNKI and Wanfang databases were searched for literatures related to the application of DL in MCI among older adults,from database inception to December,2024.A scoping review was conducted.The literature screening process followed the Scoping Review Report Specification list,and the quality assess-ment was conducted using the cross-sectional study quality evaluation tool developed by the Evidence-based Health Care Center.Results A total of eleven papers were included,from Italy,USA,South Korea,China,India and Switzerland,involving 11 829 elderly participants,publicated mainly between 2014 and 2024,reflecting the rapid development trend of the field in the last decade,which was in line with the timing of the development of DL technology.The quality scores of the included literatures were all six to seven.The types of studies were all cross-sectional studies with significant cross-disciplinary characteristics,mainly originating from the fields of clinical medicine,biology and neuroimaging.The literature data were mainly based on the Alzheimer's disease Neuroimaging Program database and integrated other data resources.In terms of data type,in addition to brain imaging data,one study based on text data was also included.In terms of models used,five of the studies were mainly based on convolutional neu-ral networks,and the rest used different DL modeling frameworks.The task types contained binary and triple classification.In terms of prediction results,the DL models constructed on multimodal data,such as brain imag-es,could be used to construct high-precision prediction models for MCI classification,and the models were all good,with accuracy more than 70%and AUC values more than 0.7.The diagnostic accuracy of some of the mod-els was more than 90%,and the model with the highest prediction accuracy was the one that used the Biceph-Net lightweight framework,with accuracy close to 100%,and the text analysis model based on Transformer made the AUC value of 0.846,which provided new ideas for the diagnosis of non-imaging data.Conclusion DL can not only provide strong support for the accurate identification of MCI in the elderly,but also provide auxiliary prediction tools for clinicians,which can help delay the progression of the disease and improve the prognosis of patients.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Objective To evaluate the methodological quality and measurement attribute quality of the evaluation tool for pediatric palliative care quality assessment tools,and to provide references for medical staff to select the best assessment tools.Methods The PubMed,Embase,Cochrane Library,Web of Science,CINAHL,Scopus,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database,Chinese Biomedical Literature Database,GIN,NGC,NICE,NRAO,medlive,WHO,AAHPM,WHPCA,APHN were searched from inception to March 28,2024.Data were screened and extracted independently by 2 researchers.The consensus-based standards for the selection of health measurement instruments(COSMIN)checklist and quality criteria were employed to evaluate the methodological quality and psychometric properties of the included pediatric palliative care quality assessment tools.Finally,recommendations were formulated based on these evaluations.Results A total of 13 articles were included,involving 9 pediatric palliative care quality assessment tools.Among them,the PICU-QODD,PaPEQu and QCPCI demonstrated good content validity and internal consistency,and are recommended as Grade A.The remaining assessment tools are recommended as Grade B or C.Conclusion The PICU-QODD,PaPEQu and QCPCI are recommended for use,but further validation of their psychometric properties is still needed.

Objective To systematically review the application and effectiveness of deep learning(DL)in diagnosis of mild cogni-tive impairment(MCI)among older adults.Methods PubMed,Web of Science,CNKI and Wanfang databases were searched for literatures related to the application of DL in MCI among older adults,from database inception to December,2024.A scoping review was conducted.The literature screening process followed the Scoping Review Report Specification list,and the quality assess-ment was conducted using the cross-sectional study quality evaluation tool developed by the Evidence-based Health Care Center.Results A total of eleven papers were included,from Italy,USA,South Korea,China,India and Switzerland,involving 11 829 elderly participants,publicated mainly between 2014 and 2024,reflecting the rapid development trend of the field in the last decade,which was in line with the timing of the development of DL technology.The quality scores of the included literatures were all six to seven.The types of studies were all cross-sectional studies with significant cross-disciplinary characteristics,mainly originating from the fields of clinical medicine,biology and neuroimaging.The literature data were mainly based on the Alzheimer's disease Neuroimaging Program database and integrated other data resources.In terms of data type,in addition to brain imaging data,one study based on text data was also included.In terms of models used,five of the studies were mainly based on convolutional neu-ral networks,and the rest used different DL modeling frameworks.The task types contained binary and triple classification.In terms of prediction results,the DL models constructed on multimodal data,such as brain imag-es,could be used to construct high-precision prediction models for MCI classification,and the models were all good,with accuracy more than 70%and AUC values more than 0.7.The diagnostic accuracy of some of the mod-els was more than 90%,and the model with the highest prediction accuracy was the one that used the Biceph-Net lightweight framework,with accuracy close to 100%,and the text analysis model based on Transformer made the AUC value of 0.846,which provided new ideas for the diagnosis of non-imaging data.Conclusion DL can not only provide strong support for the accurate identification of MCI in the elderly,but also provide auxiliary prediction tools for clinicians,which can help delay the progression of the disease and improve the prognosis of patients.

OBJECTIVE To establish a population pharmacokinetic(PopPK)model to predict the PK characteristics of GLS-010 in humans.METHODS Fifty-eight cynomolgus monkeys were used,18 of which were randomly divided into three groups and received a single intravenous infusion of GLS-010 at doses of 2,6,and 18 mg·kg-1,respectively.The rest were randomly assigned to four groups and received multiple intravenous infusions of GLS-010 at doses of 0,5,25,and 100 mg·kg-1,respectively,once a week(quaque week,qw)for five consecutive weeks.Blood samples were collected before and after administration.The concentrations of GLS-010 in the monkey serum were measured using a validated enzyme-linked immunosorbent assay,while those of anti-drug antibodies(ADA)in the cynomolgus monkey serum were determined by ultra-sensitive electrochemiluminescence immunoassay.The PK data on GLS-010 in cynomolgus monkeys was obtained,and the drug-time curves were plotted.A PopPK model was constructed using non-compartmental analysis and evaluated by goodness-of-fit plots and visual predictive checks.The constructed PopPK model was used to predict the PK characteristics in humans,which were finally compared with actual Phase Ⅰ clinical study results for validation.RESULTS The predictive results of the PopPK model were highly consistent with the actual Phase Ⅰ clinical study results.The model was able to predict the human PK characteristics under various dosing regimens,including 1 mg·kg-1 quaque 2 weeks(q2w),4 mg·kg-1(q2w),240 mg(q2w),240 mg(q3w),and 10 mg·kg-1(q2w).The predicted maximum plasma concentrations(Cmax)were 24.8,99.1,85.0,85.0,and 247.8 mg·L-1,respectively,and the AUC0-336h was 4 902.0,20 060.0,17 147.7,22 145.7(AUC0-504h),and 50 817.6 mg·h·L-1,respectively.The safety risks for the corresponding dosing regimens were 47.3,11.6,13.5,10.5,and 4.6,respectively.The predicted receptor occupancy at steady state(ROss)at Cmax,average plasma concentration(Cavg),and minimum plasma concentration(Cmin)were 38.8％,72.7％,69.4％,64.1％and 87.2％,29.1％,63.8％,60.0％,49.8％and 82.1％,21.9％,55.5％,51.3％,36.3％and 76.7％,respectively.CONCLUSION The PopPK model can effectively predict the human PK characteristics under different dosing regimens with high consistency with actual Phase Ⅰ clinical study results,which can serve as an important reference for selection of safe and effective doses for first-in-human research.

Methods: (i) Animal experiments. This study conducted experiments using specific pathogen-free (SPF) grade male C57BL/6J wild-type (WT) mice and APP/PS1 double transgenic mice. The animals were divided into three groups: WT group (WT mice, n = 5, receiving distilled water daily), APP/PS1 group (APP/PS1 double transgenic mice, n = 5, receiving distilled water daily), and BSTSD group [APP/PS1 double transgenic mice, n = 5, treated with BSTSD suspension at a dosage of 27 g/(kg·d) for 90 d]. Cognitive function was assessed using the Morris water maze (MWM). Post-experiment, hippocampal tissues were collected for analysis of pyramidal cell and synaptic morphology through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). (ii) Cell experiments. The HT-22 cells were divided into control group (untreated), Aβ25-35 group (treated with 20 μmol/L Aβ25-35 for 24 h), icariin group (pre-treated with 20 μmol/L icariin for 60 min, followed by 20 μmol/L Aβ25-35 for an additional 24 h), and icariin + LY294002 group [treated with 20 μmol/L icariin and 20 μmol/L LY294002 (an inhibitor of the phosphoinostitide 3-kinases (PI3K) signaling pathway) for 60 min, then exposed to 20 μmol/L Aβ25-35 for 24 h], and cell viability was measured. Western blot was used to detect the expression levels of synapse-associated proteins [synaptophysin (SYP) and postsynaptic density-95 (PSD-95)] and PI3K signaling pathway associated proteins [phosphorylated (p)-PI3K/PI3K, p-protein kinase B (Akt)/Akt, and p-mechanistic target of rapamycin (mTOR)/mTOR]. Results: (i) Animal experiments. Compared with APP/PS1 group, BSTSD group showed that escape latency was significantly shortened (P < 0.01) and the frequency of crossing the original platform was significantly increased (P < 0.01). Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly, nuclear staining was uniform, and vacuole-like changes were reduced after BSTSD treatment. TEM showed that the length of synaptic active zone in BSTSD treatment group was increased compared with APP/PS1 group (P < 0.01), and the width of synaptic gap was decreased (P < 0.01). (ii) Cell experiments. Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20 μmol/L (P > 0.05), and alleviated the cell viability decline induced by Aβ25-35 (P < 0.01). Western blot results showed that compared with Aβ25-35 group, the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased (P < 0.01), while the protein expression levels of SYP and PSD-95 were increased (P < 0.01). These effects were blocked by LY294002 (P < 0.01). Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD models and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.

[Abstract] [Objective] To compare and analyze the efficacy of platelet transfusion in patients with different doses, and to analyze the risk factors for platelet transfusion refractoriness. [Methods] A total of 5 827 patients who received platelet transfusion in the PLA General Hospital from May 2023 to May 2024 were selected as the research subjects, among which 4 780 patients were transfused with 1 therapeutic dose of platelets, and 1 047 patients were transfused with 0.5 therapeutic dose of platelets, and the efficacy of platelet transfusion was compared between the two groups. The effects of gender, disease type, white blood cell count before transfusion, fever, number of platelet transfusions, and platelet antibodies on platelet transfusion refractoriness were analyzed using univariate analysis, and the independent risk factors affecting platelet transfusion refractoriness were further analyzed by multivariate logistic regression. [Results] Among 4 780 patients, 3553 (74.3%) were effective and 1 227 (25.7%) were ineffective. Among 1 047 patients, 0.5 platelet infusion was effective in 755 cases (72.1%) and ineffective in 292 cases (27.9%). There was no significant difference in the effective rate of platelet transfusion between the two groups (P>0.05). Univariate analysis showed that the therapeutic effect of platelet transfusion was related to age, the number of platelet transfusion, disease type, platelet antibodies and white blood cell count before transfusion (P<0.05), while age, gender, fever and blood type were not related to the therapeutic effect of platelet transfusion (P>0.05). The results of multi-factor analysis showed that age, white blood cell count >50×10⁹/L, platelet transfusion times, disease type and platelet antibody were independent risk factors for ineffective transfusion (P<0.05). [Conclusion] There is no significant difference in the efficacy of platelet infusion with 0.5 therapeutic dose or 1 therapeutic dose. In addition, age, white blood cell count >50×10⁹/L, the number of platelet transfusion, disease type and platelet antibodies were the factors affecting the ineffective platelet transfusion in group 2.

Objective To investigate the effect of a three-tier delirium care management process in patients with acute stroke in neurology intensive care unit(NICU).Methods A total of 50 patients with acute stroke admitted to the NICU of the Fourth Hospital of Changsha from May to September 2021 were assigned to the control group.The patients in the control group received routine NICU nursing care to prevent delirium.Another 50 patients with acute stroke admitted to the NICU from December 2021 to April 2022 were assigned to the trial group.They were managed with the three-tier delirium nursing management process on top of the routine NICU nursing care for the control group.The incidence of ICU delirium(DICU),duration of DICU,length of stay in NICU and the incidence of delirium-related adverse events were compared between the two groups.The degree of delirium and cognitive function before and after the intervention were compared between the two groups as well.Results The trial group had significantly shorter duration of DICU and NICU stay(both P<0.05)and lower incidence rate of delirium-related adverse events(P<0.05)compared to the control group.After the intervention,the trial group showed significantly lower scores on the intensive care delirium screening checklist(ICDSC)and significantly higher scores of cognitive function compared to those of the control group(both P<0.05).Conclusion The three-tier delirium nursing management process can lower the occurrence of delirium in NICU patients with acute stroke,shorten the NICU stay,reduce the safety risk in nursing,and improve the cognitive function.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.