Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Objective To analyze the application characteristics,trends,and special advantages of anti-infection research using the Bayesian method,and to provide methodological reference for the development of anti-infection research.Methods PubMed,CNKI and WanFang Data were electronically searched for the studies on anti-infection using Bayesian method published from January 1,2015 to November 21,2023.The relevant information of publication time,anti-infection type,sample size,Bayesian characteristics and Bayesian application pattern were analyzed descriptively and reviewed.Results A total of 86 studies were included,of which 41.9％were observational studies,only 7.0％were enterprise-initiated studies,and 48.8％were mentioning prior information studies.There was no domestic intervention study.The application characteristics and advantages of Bayesian method in intervention study,observational study and pharmacokinetic study are different.In intervention researches and observational researches,the application of Bayesian design decision and the application of Bayesian analysis and estimation accounts for 69.2％and 52.8％at most,respectively.Conclusions The Bayesian method is flexible,can be used for small sample sizes and complex model research,and can deal with uncertainty.In intervention studies in the field of anti-infection in China,the Bayesian method has not been applied widely.Only a handful of studies applying Bayesian method have been initiated by companies.In the future,it is still necessary to promote the advantages and application scenarios of Bayesian methods in the field of anti-infection research and strengthen the standardization of the application of Bayesian method.

ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

Objective To analyze the application characteristics,trends,and special advantages of anti-infection research using the Bayesian method,and to provide methodological reference for the development of anti-infection research.Methods PubMed,CNKI and WanFang Data were electronically searched for the studies on anti-infection using Bayesian method published from January 1,2015 to November 21,2023.The relevant information of publication time,anti-infection type,sample size,Bayesian characteristics and Bayesian application pattern were analyzed descriptively and reviewed.Results A total of 86 studies were included,of which 41.9％were observational studies,only 7.0％were enterprise-initiated studies,and 48.8％were mentioning prior information studies.There was no domestic intervention study.The application characteristics and advantages of Bayesian method in intervention study,observational study and pharmacokinetic study are different.In intervention researches and observational researches,the application of Bayesian design decision and the application of Bayesian analysis and estimation accounts for 69.2％and 52.8％at most,respectively.Conclusions The Bayesian method is flexible,can be used for small sample sizes and complex model research,and can deal with uncertainty.In intervention studies in the field of anti-infection in China,the Bayesian method has not been applied widely.Only a handful of studies applying Bayesian method have been initiated by companies.In the future,it is still necessary to promote the advantages and application scenarios of Bayesian methods in the field of anti-infection research and strengthen the standardization of the application of Bayesian method.

Objective To compare the value of stack-of-stars-volumetric interpolated breath-hold examination(Star-VIBE)and T1-volumetric interpolated breath-hold examination(T1-VIBE)MRI for displaying peripheral lung cancer.Methods Fifty-two patients with 56 peripheral lung cancer were prospectively enrolled,and chest Star-VIBE and T1-VIBE MRI were acquired.The morphological features were observed,and the subjective scores were recorded.The maximum diameter,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of lesions were measured based on Star-VIBE and T1-VIBE MRI,respectively.Taken CT as the references,the value of Star-VIBE and T1-VIBE MRI for displaying peripheral lung cancer were compared.Results Star-VIBE MRI had higher scores for displaying spiculation sign,lobulation sign,pleural depression sign and halo sign than T1-VIBE(both P＜0.05).CNR and SNR of Star-VIBE MRI were significantly higher than those of T1-VIBE(both P＜0.001).No significant difference of the maximum diameter of lesions measured based on Star-VIBE and T1-VIBE MRI compared with CT was found,nor between Star-VIBE and T1-VIBE MRI(all P＞0.05).Conclusion Star-VIBE MRI had better value for displaying peripheral lung cancer than T1-VIBE.

Objective To explore the effect of hospital community integration management program on monocyte(MONO),blood uric acid(BUA),body mass index(BMI)and MONO/high density lipoprotein cholesterol ratio(MHR)in patients with hyperuricemia(HUA).Methods A total of 103 HUA patients admitted to the department of nephrology of the First Hospital of Ninghai County from January 2020 to January 2022 were chosen as the study object.The patients were divided into experimental group(51 cases,management method:hospital community integration management mode)and the control group(52 cases,management method:conventional management mode)based on the admission order(odd and even).The differences of MONO,BUA,BMI,MHR between the two groups at admission and discharge and 6,12 and 24 months after discharge were compared,and the occurrence of adverse reactions was observed.Results There were no significant differences in MONO,BUA,BMI and MHR levels at admission between the two groups,MONO,BUA,BMI and MHR levels were significantly lower at discharge and at 6,12,and 24 months after discharge compared with admission.The lowest level was reached 24 months after discharge,and the experimental group was significantly lower than the control group[MONO(×109/L):0.34(0.16)vs.0.37(0.18),BUA(μmol/L):329.7±70.5 vs.381.2±71.7,BMI(kg/m2):21.3±1.1 vs.24.2±0.9,MHR:0.24(0.16)vs.0.27(0.15),all P<0.05].The overall incidence of adverse reactions in the experimental group was significantly lower than that of control group[3.92%(2/51)vs.15.38%(8/52),P<0.05].Conclusion The scientific and reasonable implementation of integrated hospital and community management is beneficial to reduce the levels of MONO,BUA,BMI,MHR and reduce the occurrence of adverse reactions in patients.

Objective To investigate the impacts of butorphanol(BUT)on the biological activity and chemotherapy drug resistance of osteosarcoma cells by regulating the forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signal axis.Methods CDDP resistant MG-63 cells(MG-63/CDDP)treated with 2.0 μmol/L cisplatin(CDDP)were separated into control group(MG-63/CDDP cells were treated with 0.05％DMSO medium),BUT group(MG-63/CDDP cells were treated with 40 μg/mL BUT),JY-2 group(MG-63/CDDP cells were treated with 100 μmol/L FOXO3-FOXM1 inhibitor JY-2),and BUT+JY-2 group(MG-63/CDDP cells were treated with 40 μg/ml BUT and 100 μmol/L JY-2).CCK8 method was applied to detect MG-63/CDDP cell activity.Flow cytometry was used to detect apoptosis in MG-63/CDDP cells.The Transwell method was applied to detect the migration and invasion of MG-63/CDDP cells;Western blot was applied to detect the expression of autophagy proteins and proteins related to the FOXO3-FOXM1 signaling pathway.Results Compared with MG-63 cells,the IC50(20.56±2.52μmol/L vs(0.97±0.10μmol/L)of MG-63/CDDP cells was increased,and the differences was statistically significant(q=19.017,P<0.05),and the optimal concentration of 1 μmol/L CDDP was selected for subsequent experiments.Compared with the control group,the A value(0.43±0.05 vs 0.68±0.06),numbers of cell migration(63.63±7.58 vs 114.56±10.57)and invasion(43.38±4.58 vs 79.56±8.48),and the levels of autophagy-related protein Beclin1(0.31±0.05 vs 0.62±0.07)and microtubule-associated protein light chain 3(LC3)-Ⅱ/Ⅰ proteins(0.51±0.08 vs 0.98±0.11)in the BUT group were reduced(q=6.763～9.591,all P<0.05),the apoptosis rate(28.57％±3.14％vs 8.67％±1.46％),the levels of FOXO3(0.72±0.08 vs 0.33±0.04)and FOXM1(1.22±0.15 vs 0.70±0.08)proteins were increased(q=14.077,10.681,7.493,all P<0.05),however,in the JY-2 group,the A value(0.99±0.13 vs 0.68±0.06),numbers of cell migration(147.59±15.37 vs 114.56±10.57)and invasion(111.83±12.58 vs 79.56±8.48),and the levels of Beclin1(0.94±0.11 vs 0.62±0.07)and LC3-Ⅱ/Ⅰ(1.27±0.13 vs 0.98±0.11)proteins in the JY-2 group were increased(q=4.171～6.012,all P<0.05),the apoptosis rate(4.56％±0.86％vs 8.67％±1.46％),the levels of FOXO3(0.17±0.01 vs 0.33±0.04)and FOXM1(0.46±0.03 vs 0.70±0.08)proteins were reduced(q=5.941,9.505,6.881,all P<0.05),and the differences were statistically significant,respectively.JY-2 reversed the beneficial effects of BUT on MG-63/CDDP cell activity and chemotherapy resistance.Conclusion BUT may regulate the cell activity and CDDP resistance of osteosarcoma cells by activating the FOXO3-FOXM1 signaling pathway.

Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.