OBJECTIVE To investigate the mechanism of cordycepin in delaying the transformation from acute kidney injury （AKI） to chronic kidney disease （CKD） （short for “AKI-CKD”）. METHODS Network pharmacology and bioinformatics were used to analyze and predict the signaling pathways of cordycepin in delaying AKI-CKD progression and its relationship with the ferroptosis pathway. Cell experiments were performed to verify the predicted results. Human renal tubular epithelial HK-2 cells were divided into blank group， cordycepin group， model group， and H 2 O 2 +cordycepin group. Except for the blank group and cordycepin group， all other groups were treated with 150 μmol/L H 2 O 2 for 72 h to induce persistent oxidative stress injury in cells. After 72 h of cordycepin （40 μmol/L） intervention， the protein and mRNA expression levels of glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4），nuclear factor-erythroid 2-related factor 2（Nrf2）， and heme oxygenase-1 （HO-1） in cells were detected. Furthermore， the Nrf2 inhibitor ML385 was added on the basis of H 2 O 2 +cordycepin to verify the role of the Nrf2/HO-1 pathway. RESULTS Network pharmacology and bioinformatics analysis showed that there were 42 overlapping genes related to AKI-CKD and ferroptosis that interact with cordycepin ferroptosis， among which 38 were annotated as ferroptosis-related genes. HO-1 and Nrf2 might be important targets for cordycepin to inhibit ferroptosis. The binding energies of cordycepin with Nrf2 and HO-1 proteins were －8.5 and －6.7 kcal/mol， respectively. Cell experiments showed that compared with the model group， the protein and mRNA expression levels of GPX4， Nrf2 and HO-1 were significantly increased （ P ＜0.05），while the protein and mRNA expression levels of ACSL4 were significantly decrease d （ P ＜0.05） in the H 2 O 2 +cordycepin group. After the addition of the Nrf2 inhibitor ML385， the effects of cordycepin on the above proteins and mRNA were significantly reversed （ P ＜0.05）. CONCLUSIONS Cordycepin can inhibit ferroptosis by activating the Nrf2/HO-1 pathway， reduce persistent oxidative stress injury of renal tubular epithelial cells， and delay the progression of AKI-CKD.

Objective:To discuss the effect of long non-coding RNA(lncRNA)DUXAP8 in exosomes(Exo)derived from the lung cancer A549 cells on the growth and immune escape of the lung cancer cells,and to clarify the mechanism.Methods:The human lung cancer cell line A549 was cultured,and its exosomes were extracted and identified.The A549 cells were treated with PKH67-labeled Exo to observe the uptake of Exo by A549 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of lncRNA DUXAP8 in A549 cells before and after Exo treatment.The A549 cells were divided into control group(no treatment),Exo group(A549 cells treated with Exo),Exo+sh-NC group(A549 cells treated with Exo and then transfected with sh-NC),and Exo+sh-DUXAP8 group(A549 cells treated with Exo and then transfected with sh-DUXAP8).RT-qPCR method was used to detect the expression level of lncRNA DUXAP8 in A549 cells in various groups;colony formation assay was used to detect the colony formation abilities of the A549 cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining method was used to detect the proliferation abilities of the A549 cells in various groups.After co-culturing A549 cells in various groups with human peripheral blood lymphocytes,flow cytometry was used to detect the percentages of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in various groups;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)method was used to detect the killing rates of human peripheral blood lymphocytes on the A549 cells in various groups.Results:The diameter of Exo vesicles was 50-150 nm,and the exosome-specific marker proteins cluster of differentiation 63(CD63),cluster of differentiation 9(CD9),tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)were positively expressed,indicating successful exosome extraction.A549 cells efficiently took up PKH67-labeled Exo.The RT-PCR results showed that compared with A549 cells cultured alone,the expression level of lncRNA DUXAP8 in the A549 cells was increased after treatment with Exo derived from A549 cells(P<0.05).compared with control group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there were no significant difference in the expression level of IncRNA DUXAP8 in the cells in Exo+sh-NC group(P>0.05).The colony formation assay results showed that compared with control group,the number of colony formation of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the number of colony formation of the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the number of colony formation of the A549 cells in Exo+sh-NC group(P>0.05).The EdU staining results showed that compared with control group,the EdU-positive rate of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the EdU-positive rate in A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the EDU-positive rate in the cells in Exo+sh-NC group(P>0.05).The flow cytometry results showed that compared with control group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo group was decreased(P<0.05);compared with Exo group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo+sh-DUXAP8 group was increased(P<0.05),while there was no significant difference in the percentage of activated CD8+T lymphaytes in Exo+sh-NC group(P>0.05).The MTT assay results showed that compared with control group,the killing rate of human peripheral blood lymphocytes on the A549 cells in Exo group was decreased(P<0.05);compared with Exo group,the killing rate of human peripheral blood lymphocytes on A549 cells in Exo+sh-DUXAP8 group was increased(P<0.05),while no significant difference was observed in Exo+sh-NC group(P>0.05).Conclusion:The lncRNA DUXAP8 in exosomes derived from the lung cancer A549 cells promotes the proliferation of lung cancer cells and tumor immune escape.

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective:To explore the epidemiological characteristics of human metapneumovirus (hMPV) in children hospitalized for acute respiratory tract infections in Hebei, and provide a theoretical basis for the clinical diagnosis and treatment of acute respiratory tract infections in children in Hebei.Methods:Retrospectively, 41 499 children hospitalized in Hebei Children′s Hospital for acute respiratory tract infections from January 2017 to December 2021 were included to analyze the morbidity of children of different genders and ages, and in different seasons, and to statistically analyze the epidemiological data such as the positive detection rate of hMPV, the detection rates of mixed infections with other pathogens, and the clinical diagnosis.Results:The overall positive detection rate of hMPV in hospitalized children with acute respiratory infections from 2017 to 2021 was 5.94%(2 464/41 499), with the highest positive detection rate of hMPV in the age group of 3 to 4 years (7.66%, 520/6 789) and the lowest in the age group of ≥5 years (2.89%, 180/6 225), with a statistically significant difference ( P<0.001); the positive detection rates in male and female children were respectively 5.97%(1 496/25 056) and 5.94%(968/16 443), and the difference was not statistically significant ( P>0.05). The positive detection rates of hMPV from 2017 to 2021 were 5.10%(408/7 998), 9.64%(915/9 491), 4.27%(426/9 969), 5.91%(368/6 226), and 4.44%(347/7 815), respectively, and the positive detection rate of hMPV in 2018 was significantly higher than that in the other years ( P<0.001). hMPV circulated throughout the year, with obvious seasonality, with the highest positive detection rate in spring and winter.The mixed detection rate of hMPV with other respiratory pathogens was 42.74% (1 053/2 464), of which mixed detection with rhinovirus was the most common, with a mixed detection rate of 48.24%(508/1 053).Clinical diagnosis of hPMV-positive children was mostly bronchopneumonia. Conclusions:hMPV is one of the important pathogens in hospitalized children with acute respiratory infections in Hebei, which is common in children under 5 years of age and can occur throughout the year, with peak epidemics in winter and spring. Mixed infections of hMPV with other respiratory pathogens are common and can increase the risk of worsening clinical symptoms in children.

Objective:To evaluate the accuracy of L-shaped reduction malarplasty under the guidance of virtual surgical planning (VSP).Methods:The data of adult female patients who were diagnosed with zygomatic protrusion or hypertrophy at Department of Orthognathic and Temporo-mandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University, from January 2018 to December 2020 were analyzed retrospectively. L-shaped reduction malarplasty with or without bone resection and with the mortice and tenon joint structure on the zygomatic arch was conducted either by digital procedures comprising VSP and three-dimensional printing titanium templates (digtal surgery group) or by conventional method (control group). The incidence of postoperative complications and the patient postoperative satisfaction [using a Likert scale with a score ranging from 1 to 5, representing very dissatisfied, dissatisfied, average, satisfied and very satisfied, satisfaction rate = (very satisfied + satisfied)/ total number of patients × 100%] were statistically analyzed in the two groups. The differences in the postoperative symmetry of the zygomatic complex between the digital group and the control group were analyzed by three-dimensional cephalometry. The accuracy of VSP in L-shaped reduction malarplasty was evaluated by comparing the preoperative design model with the actual postoperative model in the digital group. The statistical analyses were conducted using SPSS 24.0 software. The chi-square test was used in the comparison of surgical complications and patient satisfaction rates. The symmetry of bilateral landmarks in the three-dimensional direction between the two groups was evaluated using the independent t-test, and the pre- and post-operative measurements in the digital group were compared using paired t-test. Results:A total of 78 patients were included, with 36 in the digital group, aged (25.2±3.6) years, and 42 in the control group, aged (24.3±2.8) years. Satisfactory reduction of zygomatic protrusion or hypertrophy was recognized among all patients. Compared with the control group, the digital group had lower percentage of complications [25% (9/36) vs. 55% (23/42)] and higher postoperative satisfaction [78% (28/36) vs. 48% (20/42)], both of which were statistically significant (all P<0.01). Regarding the symmetry of bilateral zygomatic complexes, the average deviations of ΔZb (bottom point of zygoma) in the digital group in the horizontal, vertical, and sagittal directions [(1.05±0.24), (1.05±0.24), (1.00±0.88) mm] were significantly smaller than those in the control group [(2.03±0.58), (1.32±0.68), (1.47±0.47) mm], with statistically significant differences (all P<0.05). The bone segment movements of virtual plans and actual result in the digital surgery group were measured and showed no obvious difference for the inward movement [(5.42±0.98) mm vs. (5.33±0.93) mm] and the sagittal overlap [(4.87±1.21) mm vs. (4.77±1.32) mm] at the zygoma roots, along with the step length at the long-arm of the L-shaped osteotomy line [(2.43±1.11) mm vs. (2.39±0.89) mm] (all P>0.05). The mean differences of facial width and protrusion measurements between virtual simulations and actual result in the digital group ranged from (1.13±0.47) mm to (2.07±0.88) mm, with no significant differences( P>0.05). Meanwhile, the high resemblance between virtual plans and actual result was depicted via superimposition models, with a deviation controlled within ±0.5 mm. Conclusion:The application of VSP in reduction malarplasty significantly improved surgical accuracy and reduced difficulties in the operation, which would improve patients’ postoperative satisfaction.

Objective To explore the effects of 1 800 MHz electromagnetic radiation(EMR)on cognitive function of 3xTg-AD and 57C mice,providing a theoretical basis for the potential impacts of electromagnetic radiation on the human body.Methods A total of 12 3xTg-AD transgenic mice and 12 wild-type C57 mice were selected as research subjects.The one-month-old mice were divided into four groups:RF WT,Control WT,RF AD,and Control AD,with 6 mice in each group.The 1 800 MHz EMR exposure experiments were conducted from 20:00 to 8:00 the next day for a duration of 5 months.After the exposure,a water maze test was conducted to evaluate the effects of EMR on spatial learning and memory abilities of 3xTg AD mice,along with measurements of body weight,brain weight,and calculation of the brain-to-body ratio.Finally,Western Blot technique was used to measure the levels of APP,NR1,and NR2A in hippocampal tissue to analyze effects of 1 800 MHz EMR on the cognitive function of 3xTg AD mice.Results Under 1 800 MHz EMR exposure,there were no statistically significant differences in Morris water maze spatial learning ability among the four groups(P>0.05).However,longer escape time,greater swimming distances,and more crossings of target quadrant were exhibited in the RF AD group compared to the other groups(P<0.05).Western Blot results showed that the APP protein levels in 3xTg AD mice was higher than those in C57 mice(P<0.05).The expression levels of NR1 protein in the WT group was higher than those in the AD group(P<0.05);in the AD group,the RF AD group had higher levels than the Control WT group(P<0.05),and the NR2A protein levels in the Control WT group were higher than in the other groups(P<0.05).Conclusion Prolonged exposure to 1 800 MHz EMR can affect the learning and cognitive function of both 3xTg AD and C57 mice.

Objective To develop an ICU patient care difficulty index based on psychosocial factors and to evaluate its reliability and validity,thereby providing a comprehensive tool for assessing the difficulties in ICU patient care.Methods Guided by Guarinoni theory,an index system was developed through systematic literature reviews,semi-structured interviews,two rounds of Delphi expert consultation and the analytic hierarchy process.Based on the drafted system,a questionnaire was formulated.The tests for validity and reliability were conducted on 290 patients selected by convenience sampling.Results The finalised ICU patient care difficulty index system was composed of 5 primary indices(the general condition of the patient,disease condition,nursing condition,social support,and organizational characteristics),13 secondary indices and 27 tertiary indices.The Kendall's coefficient of coordination W values were 0.380 and 0.498,respectively,indicating a statistically significant agreement(both P<0.001).The system demonstrated a robust reliability(Cronbach's α=0.896)and a good internal consistency.Validity was confirmed through a scale level-content validity index(S-CVI)of 0.94 and the item level-content validity indices(I-CVI)ranged from 0.87 to 1.00.Structural validity analysis,based on 8 extracted public factors,showed a cumulative variance contribution rate of 66.34%.Conclusion The ICU patient care difficulty index system shows a high reliability and validity,making it a valuable tool for accurately quantification of the difficulty in ICU patient care.This system provides a scientific basis for allocation of ICU nursing resource and performance distribution.

Objective:To retrieve, appraise and synthesize evidence regarding the prevention and management of high-output ileostomy in post-enterostomy patients, thereby providing a scientific reference for clinical practice.Methods:A computerized search was conducted, systematically exploring national and international databases, as well as the websites of pertinent associations, to gather evidence relevant to the topic. The literature types included clinical decision-making, evidence summaries, guidelines, expert consensus, and systematic reviews. The search timeframe was established from the date of database construction until 23 August 2024. The methodological quality assessment of the literature, along with the extraction and synthesis of the evidence, was performed by two independent researchers utilizing established criteria and adhering to rigorous standards.Results:A total of 13 papers were included in the review, comprising one clinical decision, four guidelines, and eight systematic reviews. Eighteen pieces of best evidence were distilled and summarized across six key areas: diagnosis and risk identification, fluid/diet/nutrition management, medication administration, skin management, monitoring and health education, and follow-up care.Conclusions:The clinical practice rationale for the prevention and management of high-output ileostomy in post-enterostomy patients, when summarized, would offer scientific and effective evidence-based support for practice changes by clinical care staff. The practical application and translation of this evidence should thoroughly consider the nuances of clinical practice in China, as well as individual patient differences, to ensure the effective implementation of the best evidence for maximizing patient benefit.

Objective To develop an ICU patient care difficulty index based on psychosocial factors and to evaluate its reliability and validity,thereby providing a comprehensive tool for assessing the difficulties in ICU patient care.Methods Guided by Guarinoni theory,an index system was developed through systematic literature reviews,semi-structured interviews,two rounds of Delphi expert consultation and the analytic hierarchy process.Based on the drafted system,a questionnaire was formulated.The tests for validity and reliability were conducted on 290 patients selected by convenience sampling.Results The finalised ICU patient care difficulty index system was composed of 5 primary indices(the general condition of the patient,disease condition,nursing condition,social support,and organizational characteristics),13 secondary indices and 27 tertiary indices.The Kendall's coefficient of coordination W values were 0.380 and 0.498,respectively,indicating a statistically significant agreement(both P<0.001).The system demonstrated a robust reliability(Cronbach's α=0.896)and a good internal consistency.Validity was confirmed through a scale level-content validity index(S-CVI)of 0.94 and the item level-content validity indices(I-CVI)ranged from 0.87 to 1.00.Structural validity analysis,based on 8 extracted public factors,showed a cumulative variance contribution rate of 66.34%.Conclusion The ICU patient care difficulty index system shows a high reliability and validity,making it a valuable tool for accurately quantification of the difficulty in ICU patient care.This system provides a scientific basis for allocation of ICU nursing resource and performance distribution.

Objective:To evaluate the accuracy of L-shaped reduction malarplasty under the guidance of virtual surgical planning (VSP).Methods:The data of adult female patients who were diagnosed with zygomatic protrusion or hypertrophy at Department of Orthognathic and Temporo-mandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University, from January 2018 to December 2020 were analyzed retrospectively. L-shaped reduction malarplasty with or without bone resection and with the mortice and tenon joint structure on the zygomatic arch was conducted either by digital procedures comprising VSP and three-dimensional printing titanium templates (digtal surgery group) or by conventional method (control group). The incidence of postoperative complications and the patient postoperative satisfaction [using a Likert scale with a score ranging from 1 to 5, representing very dissatisfied, dissatisfied, average, satisfied and very satisfied, satisfaction rate = (very satisfied + satisfied)/ total number of patients × 100%] were statistically analyzed in the two groups. The differences in the postoperative symmetry of the zygomatic complex between the digital group and the control group were analyzed by three-dimensional cephalometry. The accuracy of VSP in L-shaped reduction malarplasty was evaluated by comparing the preoperative design model with the actual postoperative model in the digital group. The statistical analyses were conducted using SPSS 24.0 software. The chi-square test was used in the comparison of surgical complications and patient satisfaction rates. The symmetry of bilateral landmarks in the three-dimensional direction between the two groups was evaluated using the independent t-test, and the pre- and post-operative measurements in the digital group were compared using paired t-test. Results:A total of 78 patients were included, with 36 in the digital group, aged (25.2±3.6) years, and 42 in the control group, aged (24.3±2.8) years. Satisfactory reduction of zygomatic protrusion or hypertrophy was recognized among all patients. Compared with the control group, the digital group had lower percentage of complications [25% (9/36) vs. 55% (23/42)] and higher postoperative satisfaction [78% (28/36) vs. 48% (20/42)], both of which were statistically significant (all P<0.01). Regarding the symmetry of bilateral zygomatic complexes, the average deviations of ΔZb (bottom point of zygoma) in the digital group in the horizontal, vertical, and sagittal directions [(1.05±0.24), (1.05±0.24), (1.00±0.88) mm] were significantly smaller than those in the control group [(2.03±0.58), (1.32±0.68), (1.47±0.47) mm], with statistically significant differences (all P<0.05). The bone segment movements of virtual plans and actual result in the digital surgery group were measured and showed no obvious difference for the inward movement [(5.42±0.98) mm vs. (5.33±0.93) mm] and the sagittal overlap [(4.87±1.21) mm vs. (4.77±1.32) mm] at the zygoma roots, along with the step length at the long-arm of the L-shaped osteotomy line [(2.43±1.11) mm vs. (2.39±0.89) mm] (all P>0.05). The mean differences of facial width and protrusion measurements between virtual simulations and actual result in the digital group ranged from (1.13±0.47) mm to (2.07±0.88) mm, with no significant differences( P>0.05). Meanwhile, the high resemblance between virtual plans and actual result was depicted via superimposition models, with a deviation controlled within ±0.5 mm. Conclusion:The application of VSP in reduction malarplasty significantly improved surgical accuracy and reduced difficulties in the operation, which would improve patients’ postoperative satisfaction.