To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

OBJECTIVE To assess the safety profile of sintilimab in combination with chemotherapy for the treatment of cholangiocarcinoma. METHODS The data of patients with cholangiocarcinoma from January 1st， 2021 to December 31st， 2022 were collected and divided into control group （29 cases） and observation group （18 cases） based on different medication regimens. Patients in the control group were treated with Gemcitabine hydrochloride for injection+Cisplatin for injection or Oxaliplatin for injection， the observation group was treated with Sintilimab injection based on the control group. Patients in each group underwent blood routine， liver and kidney function， biochemical and other examinations before and after each treatment cycle to observe the occurrence of adverse drug reactions. The correlation of adverse drug reactions with drugs was evaluated with Naranjo’s scale. RESULTS The correlation between blood toxicity and drug use was deemed “probable” in both groups； however， the observation group exhibited a significantly higher score， indicating a stronger correlation. In the control group， hepatotoxic reactions were classified as “suspicious” whereas in the observation group， they were categorized as “probable”. The correlation of gastrointestinal symptoms between the two groups was considered “possible”. Systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity and renal toxicity were all classified as having a “suspicious” correlation with drug use. The total incidence of blood toxicity in the observation group was significantly higher than control group （P＝0.014）. There was no statistically significant difference in the total incidences of hepatotoxic， gastrointestinal symptoms， systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity， renal toxicity， or the incidence of grade 3 or higher blood toxicity， hepatotoxic between the two groups （P＞0.05）. For the patients experiencing adverse drug reactions， the symptoms were alleviated following drug discontinuation or symptomatic supportive treatment. No fatalities occurred during the treatment period. CONCLUSIONS Sintilimab combined with chemotherapy may significantly increase the risk of blood toxicity in patients with cholangiocarcinoma， especially thrombocytopenia， but the adverse reactions are within a controllable range， and the overall safety is good.

ObjectiveTo explore the possible mechanism of Yigan Fupi Prescription （抑肝扶脾方， YFP） in treating diarrhea-type irritable bowel syndrome （IBS-D） by investigating the AKT/mTOR signaling pathway. MethodsSixty SD rats were randomly divided into control group， model group， YFP low-， medium-， and high-dose group， and pinaverium bromide group， with 10 rats in each group. All groups but the control group， were subjected to 21 days of tail-clamping stimulation and 14 days of senna leaf gavage to establish a liver stagnation and spleen deficiency-type IBS-D rat model. After successful modeling， the YFP low-， medium-， and high-dose group were administered 0.96， 1.93， and 3.87 g/（kg·d） of the prescription， respectively. The pinaverium bromide group was given 13.5 mg/（kg·d）， while the control and model groups were given 10 ml/（kg·d） distilled water. All groups were administered once daily for 14 consecutive days. General conditions of the rats were recorded during the experiment， and after modeling and drug administration， body weight， Bristol stool score， abdominal withdrawal reflex （AWR） score， and histo pathology of colon tissue were observed under HE staining. ELISA was used to detect serum levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Immunofluorescence was employed to detect the levels of AKT/mTOR pathway-related proteins including phosphorylated AKT （p-AKT）/AKT and phosphorylated mTOR （p-mTOR）/mTOR in the colon tissue. Western Blotting was used to detect the levels of autophagy-related proteins， including UNC-51-like kinase 1 （ULK1）， Beclin1 and LC3， and tight junction proteins including Occludin and ZO-1 in the colon tissue. ResultsAfter modeling， compared to the control group， the body weight of rats in the other groups decreased， and Bristol stool scores， as well as AWR scores under 20， 40， 60， and 80 mmHg increased （P＜0.05 or P＜0.01）. After drug administration， compared to the control group， the model group showed reduced body weight， decreased ULK1， Beclin1， LC3Ⅱ/LC3Ⅰ， Occludin， and ZO-1 protein levels in the colon tissue （P＜0.05 or P＜0.01）， and increased Bristol stool scores， AWR scores， serum TNF-α， IL-1β， and IL-6 levels， as well as p-AKT/AKT and p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. Pathological results showed a significant reduction in goblet cells in the upper part of the glandular layer of the colon， with mild inflammatory cell infiltration. The submucosal collagen fibers were dissolved， with unclear boundaries， pale staining， and microvascular congestion and dilation. Compared with the model group， the YFP low-， medium-， and high-dose group and the pinaverium bromide group showed increased body weight， Beclin1， Occludin， and LC3Ⅱ/LC3Ⅰ protein levels （P＜0.05 or P＜0.01）， and decreased Bristol stool scores， AWR scores under 40， 60， and 80 mmHg， serum IL-1β， IL-6， TNF-α levels， and p-AKT/AKT， p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. The pathological morphology of the rats in the YFP groups and pinaverium bromide group showed varying degrees of improvement. Compared with the pinaverium bromide group， the YFP low- and medium-dose group showed increased AWR scores under 20， 40， and 60 mmHg （P＜0.05）. The YFP low-dose group had reduced TNF-α， IL-1β， and IL-6 levels， and increased p-mTOR/mTOR protein relative expression levels occured in all YFP groups （P＜0.05）. Compared with the YFP low-dose group， the YFP high-dose group and pinaverium bromide group showed decreased AWR scores under different pressure levels and reduced p-AKT/AKT protein relative expression levels， while the YFP medium- and high-dose group had elevated serum TNF-α， IL-1β levels and reduced p-mTOR/mTOR protein relative expression levels （P＜0.05）. ConclusionYFP can effectively improve the pathological injury of colon tissue in IBS-D model rats with liver stagnation and spleen deficiency， reduce Bristol stool and AWR scores， and its mechanism may be related to reducing level of inflammatory factors and inhibiting AKT/mTOR pathway-related proteins in colon tissue， thereby enhancing the expression of autophagy-related proteins in the colon tissue.

Objective To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty(PKP)of vertebrae following local anesthesia.Methods From August 2019 to June 2021,118 patients with thora-co lumbar osteoporotic fractures were treated and divided into observation group and control group,with 59 patients in each gruop.In observation group,there were 26 males and 33 females,aged from 57 to 80 years old with an average of(67.69±4.75)years old;14 patients on T11,12 patients on T12,18 patients on L1,15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group.In control group,there were 24 males and 35 females,aged from 55 to 77 years old with an average of(68.00±4.43)years old;19 patients on T11,11 patients on T12,17patients on L1,12 patients on L2;the same amount of normal saline was injected intramuscularly in control group.Observation indicators included operation time,intraoperative bleeding,visual analogue scale(VAS)evaluation and recording of preoperative(T0),intraoper-ative puncture(T1),and working cannula placement(T2)between two groups of patients,at the time of balloon dilation(T3),when the bone cement was injected into the vertebral body(T4),2 hours after the operation(T5),and the pain degree at the time of discharge(T6);adverse reactions such as dizziness,nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery.Results All patients were successfully completed PKP via bilateral pedicle ap-proach,and no intravenous sedative and analgesic drugs were used during the operation.There was no significant difference in preoperative general data and VAS(T0)between two groups(P＞0.05).There was no significant difference in operation time and intraoperative blood loss between the two groups(P＞0.05).VAS of T1,T2,T3,T4 and T5 in observation group were all lower than those in control group(P＜0.05),and there was no significant difference in T6 VAS(P＞0.05).T6 VAS between two groups were significantly lower than those of T0,and the difference was statistically significant(P＜0.05).There was no signifi-cant difference in incidence of total adverse reactions between two groups(P＞0.05).There was a statistically significant differ-ence in the acceptance of repeat PKP surgery(P＜0.05).Conclusion Half an hour before operation,intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia,which could increase the comfort of patients during operation and 2 hours after operation,and improve patients satisfaction with surgery.

Objective To investigate the clinical effect of minimally invasive transforaminal lumbar interbody fusion(Mis-TLIF)technique combined with preoperative position reduction in the treatment of spondylolisthesis and summarize its advan-tages.Methods Between July 2016 and July 2022,60 patients with lumbar isthmic spondylolisthesis were retrospectively ana-lyzed,including 26 males and 34 females,with an average age of(51.32±4.24)years old ranging from 35 to 72 years old.They were divided into observation group and control group according to the operation methods.There were 30 patients in the obser-vation group,including 12 males and 18 females;the age ranged from 35 to 71 years old with an average of(51.80±6.38)years old,the course of disease ranged from 12 to 60 months with an average of(24.17±1.98)months;there were 18 cases of L4 spondylolisthesis and 12 cases of L5 spondylolisthesis;according to Meyerding classification,there were 20 cases of grade Ⅰspondylolisthesis and 10 cases of grade Ⅱ.The observation group was treated with preoperative postural reduction combined with intraoperative reduction assisted minimally invasive transforaminal lumbar fusion via Quadrant channel(Mis-TLIF).There were 30 patients in the control group,including 14 males and 16 females,with an average of(50.00±4.24)years old ranging from 36 to 72 years old;the course of disease ranged from 12 to 60 months with an average of(23.70±1.53)months;there were 16 cases of L4 spondylolisthesis and 14 cases of L5 spondylolisthesis;according to Meyerding classification,there were 19 cases of grade Ⅰ spondylolisthesis and 11 cases of grade Ⅱ.The control group was treated with open transforaminal lumbar interbody fusion(Open-TLIF).The differences of operation time,intraoperative and postoperative blood loss,hospital stay,radiation exposure time and complications between the two groups were analyzed.Visual analogue scale(VAS),Oswestry disability index(ODI)and Japanese Orthopaedic Association(JOA)score were used to evaluate the clinical effect.X-ray and CT were followed up to evaluate the interbody fusion.Results All patients were followed up for 12 months.There was no signifi-cant difference in operation time,VAS of low back pain,slip angle and slip rate between two groups(P＞0.05).The intraoperative and postoperative blood loss in the observation group(165.50±15.56)ml and(59.17±10.59)ml were less than those in the con-trol group(259.33±35.32)ml and(165.33±29.56)ml(P＜0.05).The length of hospital stay in the observation group(3.53±0.68)days was less than that in the control group(5.20±0.41)days(P＜0.05).The intervertebral space height,slip angle,slip rate,ODI,VAS and JOA scores were significantly improved in the two groups at the final follow-up(P＜0.05).There were signifi-cant differences in ODI[(9.93±1.11)％vs(10.93±1.11)％]and JOA[(26.07±1.01)points vs(25.43±1.25)points]between the observation group and the control group at the final follow-up(P＜0.05).Conclusion In the treatment of spondylolisthesis,preoperative position reduction combined with intraoperative reduction assisted Mis-Tlif technique has advantages of less trau-ma,less bleeding and shorter hospitalization period than traditional open surgery.It is a safe and effective technique.

Objective:To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia(AML).Methods:The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group,and the children with high-risk AML who received idarubicin regimen were enrolled as controls,and their clinical data were analyzed.Time to bone marrow recovery,the complete remission rate of bone marrow cytology,the clearance rate of minimal residual disease,and treatment-related adverse reactions were compared between the two groups.Results:The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day),granulocytes(18 vs 24 day),platelets(17 vs 24 day),and hemoglobin(20 vs 26 day)compared with those treated with idarubicin,there were statistical differences(P＜0.05).The effective rate and MRD turning negative rate in the observation group were 90.9％and 72.7％,respectively,while those in the control group were 94.1％and 76.4％,with no statistical difference(P＞0.05).The overall response rate of the two groups of patients was similar.Conclusion:The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML,but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

Objective:To investigate the prognostic value of minimal residual disease(MRD)detected by multi-parameter flow cytometry(MFC)in pediatric patients with acute myeloid leukemia(AML)after induction chemotherapy.Methods:A retrospective study was conducted on 97 pediatric patients initially diagnosed with AML at Wuhan Children's Hospital from August 2015 to December 2022.The study analyzed the results of MRD detection using MFC after the first and second cycles of induction chemotherapy,and its association with prognosis were analyzed.Results:Following the first cycle of induction treatment,57 of the 97 patients tested positive for MRD(MRD1+,58.8％).Subsequently,19 patients remained MRD positive(MRD2+,19.6％)after the second cycle of induction treatment.Kaplan-Meier survival analysis showed that the estimated 3-year overall survival(OS)rate of the 37(64.9％)MRD1+patients who underwent transplantation was significantly higher than that of the 20(35.1％)MRD1+patients who did not undergo transplantation(84.6％vs 40.0％,P=0.0001).Among the 35 MRD1+MRD2-patients,the 3-year OS rate of the 25 children who underwent transplantation was higher than that of the 10 children who did not undergo transplantation(87.2％vs 70.0％,P=0.3229).The 3-year OS rate of the 19 MRD1+MRD2+patients was lower than that of the 35 MRD1+MRD2-patients(57.4％vs 81.8％,P=0.059).In the 19 MRD2+patients,the 3-year OS rate of the 12 children who underwent transplantation was significantly higher than that of the 7 children who did not undergo transplantation(80.8％vs 14.3％,P=0.0007).There was no significant difference in 3-year OS between the 12 MRD1+MRD2+patients and 25 MRD1+MRD2-patients,both treated with transplantation(80.8％vs 87.2％,P=0.8868).In those not treated with transplantation,the 7 MRD1+MRD2+patients had a significantly lower 3-year OS compared with the 10 MRD1+MRD2-patients(14.3％vs 70.7％,P=0.0114).Further multivariate analysis indicated that MRD2 positivity and transplantation were both independent prognostic factors(P=0.031,0.000),while MRD1 positivity was not significantly associated with the overall prognosis of 97 patients(P=0.902).Conclusion:MRD positivity following the second cycle of induction chemotherapy is an independent risk factor for unfavorable outcomes in children with AML.MRD2 positivity indicates a poorer prognosis and can help to identify the candidates requiring transplantation.MRD2 positivity is not a contraindication for transplantation in pediatric patients,and early transplantation significantly improves the prognosis of high-risk patients.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14％)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.