Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations / 中国当代儿科杂志

OBJECTIVES@#To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children.@*METHODS@#A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed.@*RESULTS@#Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered.@*CONCLUSIONS@#Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.

Xuebijing alleviates LPS-induced acute lung injury by downregulating pro-inflammatory cytokine production and inhibiting gasdermin-E-mediated pyroptosis of alveolar epithelial cells / 中国天然药物

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Analysis of clinical characteristics and adverse events related factors in patients with giant cell arteritis / 中华风湿病学杂志

Objective:To identify the clinical characteristics and adverse events of patients with giant cell arteritis (GCA).Methods:Patients who were hospitalized and diagnosed with GCA in Zhongshan Hospital, Fudan University, from December 2009 to November 2020 were enrolled into a retrospective study analysis. Baseline data and follow-up data were collected. Adverse events were defined as one of the following events: relapses, ischemic complications and death. Patients with adverse events were analyzed in clinical features and risk factors by univariate and multivariate analysis. Associations with adverse events were assessed using ROC curve and survival curves.Results:A total of 69 patients with GCA were included in this study, with the male: female ratio of 1∶1.03. Fatigue and headache were common symptoms. Finally, 61 patients were followed up at the end of May in 2021. Over the mean follow-up time of (35±20) months, adverse events occurred in 16 cases (26.2%). Patients with adverse events had significantly lower levels of platelet and globulin at baseline than those without adverse events [(325±142)×10 9/L vs (238±112)×10 9/L, t=2.22, P=0.030]; [(31±6) g/L vs (26±6) g/L, t=2.74, P=0.008]. Red cell volume distribution width-coefficient of variation (RDW-CV) was considered an independent risk factor for adverse events [ OR (95% CI)=0.32 (0.14,0.74), P=0.008]. Further, patients especially with RDW-CV<14.75% were prone to have adverse events, which occurred in 2.6%, 20.5%, 25.6%, 33.3%, 41.00% in 1, 2, 3, 5, 10 years. Its risk increased significantly after 2 years ( P=0.042, P=0.021, P=0.002, P=0.001). The incidence of adverse events was much higher in patients with RDW-CV<14.75%(95% CI=0.002). Conclusion:Adverse events are common in patients with GCA. RDW-CV is an independent risk factor for having adverse events. Low level of RDW-CV predicts an increased risk of adverse events by the following years.

Electroacupuncture at / 中国针灸

OBJECTIVE@#To evaluate the clinical therapeutic effect of electroacupuncture (EA) at @*METHODS@#The data of 318 patients undergoing anal fistula surgery were analyzed retrospectively. In accordance with whether accepted the combined treatment with EA at bilateral @*RESULTS@#For VAS score, there was an interaction between therapeutic method and treatment duration (@*CONCLUSION@#Electroacupuncture at

Comparing the clinical characteristics and prognosis of seropositive and seronegative rheumatoid arthritis patients in China: a real-world study / 中华风湿病学杂志

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Application of "process management and evaluation" in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture- moxibustion speciality / 中国针灸

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (

Simple and robust differentiation of Ganoderma species by high performance thin-layer chromatography coupled with single quadrupole mass spectrometry QDa / 中国天然药物

In this study, a high performance thin-layer chromatography/single quadrupole mass spectrometry QDa (HPTLC-QDa) method for robust authentication of Ganoderma lucidum, a popular and valuable herbal medicine, has been developed. This method is simple and practical, which allows direct generation of characteristic mass spectra from the HPTLC plates automatically with the application of in situ solvent desorption interface. The HPTLC silica gel plates were developed with toluene-ethyl formate-formic acid (5 : 5 : 0.2, V/V) and all bands were transferred to QDa system directly in situ using 80% methanol with 0.1% formic acid as desorption solvent. The acquired HPTLC-QDa spectra showed that luminous yellow band b3, containing ganoderic acid B/G/H and ganodeneric acid B, the major active components of Ganoderma, could be found only in G. lucidum and G. lucidum (Antler-shaped), but not in G. sinense and G. applanatum. Moreover, bands b13 and b14 with m/z 475/477 and m/z 475/491/495, respectively, could be detected in G. lucidum (Antler-shaped), but not in G. lucidum, thus allowing simple and robust authentication of G. lucidum with confused species. This method is proved to be simple, practical and reproducible, which can be extended to analyze other herbal medicines.

Research advances in the pathogenesis and treatment of neurodegeneration with brain iron accumulation / 中国当代儿科杂志

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic degenerative diseases caused by genetic mutations and characterized by iron deposition in the central nervous system, especially in the basal ganglia, with an overall incidence rate of 2/1 000 000-3/1 000 000. Major clinical manifestations are extrapyramidal symptoms. This disease is presently classified into 14 different subtypes based on different pathogenic genes, and its pathogenesis and treatment remain unclear. This article summarizes the research advances in the pathogenesis and treatment of NBIA, so as to help pediatricians understand this disease and provide a reference for subsequent research on treatment.

Effect of Self-warming Blankets on Intravascular Hypothermia for Severe Traumatic Brain Injury / 中国康复理论与实践

Objective:To investigate the effect of constant temperature blankets on intravascular hypothermia for severe traumatic brain injury (sTBI). Methods:A total of 112 inpatients with sTBI from January, 2013 to December, 2018 were reviewed. They were divided into control group (n = 58) and observation group (n = 54) according to whether a self-warming blanket was used. They were assessed with Bedside Shivering Assessment Scale (BSAS). Their dosages of anti-shivering medicine, coagulation and intracranial pressure were recorded. The scores of Glasgow Outcome Scale Extended (GOSE) and the mortality one, six and twelve months after discharge were observed. Results:The incidence and severity were less in the observation group than in the control group (χ2 = 16.212, P < 0.01). The dosage of anti-shivering medicine was less in the observation group than in the control group (t > 1.269, P < 0.05). The hypercoagulation relieved significantly six hours after hypothermia in the observation group, and it was stable twelve hours after hypothermia. For the control group, the hypercoagulation relieved significantly twelve hours after hypothermia, and it was stable 24 hours after hypothermia. The intracranial pressure decreased more in the observation group than in the control group. The GOSE score and the mortality were less in the observation group than in the control group (t > 1.168, P < 0.05) one, six and twelve months after discharge. Conclusion:Application of self-warming blankets in intravascular hypothermia for sTBI may relieve shivering, hypercoagulation and intracranial pressure, to improve the outcome of patients.

Effect of miRNA-33 on ABCA1/ABCG1 expression in RAW264.7 macrophage-derived foam cells after Hcy treatment / 中国病理生理杂志

AIM:To study whether homocysteine (Hcy) inhibits the expression of ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) by microRNA-33 (miRNA-33) signaling, and reduces the efficiency of reverse cholesterol transport (RCT).METHODS:RAW264.7 macrophages were induced by oxidized low-density lipoprotein (ox-LDL) to establish foam cell model.Oil red O staining was used to determine whether the model was established successfully.miRNA-33 mimics and miRNA-33 inhibitor were transfected into the cells by Lipofectamine 2000, and the cells were exposed to Hcy at concentration of 5 mmol/L for 24 h.The intracellular lipid droplets were observed by Oil red O staining.The expression of ABCA1 and ABCG1 at mRNA and protein levels was determined by real-time PCR and Western blot.The cellular cholesterol content was analyzed by HPLC, and effluent rate of cholesterol was detected by the method of liquid scintillation counting.RESULTS:Compared with blank control group, the lipid content in miRNA-33 mimics group was increased, and the expression of ABCA1 and ABCG1 at mRNA and protein levels was decreased (P<0.05).The intracellular cholesterol content was increased gradually (P<0.05) , and the cellular cholesterol efflux rate was gradually decreased (P<0.05) in miRNA-33 mimics group.Compared with blank control group, the testing results in miRNA-33 inhibitor group were the opposition of those in miRNA-33 mimics group (P<0.05).No difference of the above indexes among blank control group, miRNA-33 mimics-NC group and miRNA-33 inhibitor-NC group was observed.CONCLUSION:Hcy inhibits the mRNA and protein expression of ABCA1 and ABCG1 through miRNA-33 signaling, and reduces the efficiency of RCT in RAW264.7 macrophage-derived foam cells.

An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels / 中华血液学杂志

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Neuroprotective effect of ticagrelor against global cerebral ischemia/reperfusion injury in rats / 中国药理学通报

Aim: To research the neuroprotective effect of ticagrelor against global cerebral ischemia/reperfusion injury in rats. Methods: Fifty adult male Wistar rats were randomly divided into five groups; sham-operation, vehicle, ticagrelor of 3 doses (37.5, 75, 150 mg · kg-1, ig). The global cerebral ischemia was established with four-vessel occlusion. Apoplexy index and neurological symptoms were detected after reperfusion injury 2 h, 24 h, 48 h. HE staining and Nissl staining were applied to assess the neuronal injury after global cerebral ischemia/reperfusion injury in CA1 region of hippocampus. Platelet aggregation induced by ADP in rats was measured with turbidimetric method. Four items of coagulation were detected by automatic coagulation analyzer. Results: Compared with vehicle, the low, medium and high doses of ticagrelor reduced the apoplexy index at 24h (P <0. 05), 48 h(P < 0. 01), and significantly reduced the neurological symptom at 48 h (P < 0. 01), and could significantly reduce platelet aggregation of rats (P < 0. 01), the number of neurons in CA1 region of hippocampus was larger (P < 0. 01), and it also significantly protected the neurons in both number and morphology. Conclusions: The ticagrelor possesses neuroprotective effect against global cerebral ischemia/reperfusion injury in rats, and it may be as a drug of neuroprotective agent in further study.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation / 中华医学杂志(英文版)

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

Long-term quality of life after sepsis and predictors of quality of life in survivors with sepsis / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To evaluate the quality of life among survivors after sepsis in 2 years, comparing with critical patients without sepsis and the general people, analyze the changes and the predictors of quality of life among septic survivors.</p><p><b>METHODS</b>This prospective case-control study screened the intensive care unit (ICU) patients in Tianjin Third Central Hospital from January 2014 to October 2017, and the Chinese general population in the previous studies was also included. According to inclusion criteria and exclusion criteria, 306 patients with sepsis were enrolled as the observation group, and another 306 patients without sepsis in ICU during the same period, whose ages, gender and Charlson Comorbidity Index matched with observation group, were enrolled as the control group. At 3 mo, 12 mo, and 24 mo after discharge, the Mos 36-item Short Form Health Survey (SF-36), the Euroqol-5 dimension (EQ-5D), and the activities of daily living (ADL) were evaluated in face-to-face for the quality of life among survivors.</p><p><b>RESULTS</b>There were 210 (68.6%) septic patients and 236 (77.1%) non-septic critically ill patients surviving. At 3 months after discharge, the observation and control groups had the similar demographic characteristics (age: 58.8 ± 18.1years vs. 57.5 ± 17.6 years, p = 0.542; male: 52.0% vs. 51.4%, p = 0.926). However, the observation group had higher acute physiology and chronic health evaluation II (APACHEII) scores, higher sequential organ failure assessment (SOFA) scores, longer hospital stay, and longer ICU stay than the control group did (p < 0.05). There were no significant differences in the eight dimensions of the SF36 scale, the EQ-5D health utility scores, and the activities of daily life scores between septic survivors and non-septic survivors (p > 0.05). In addition, compared with the quality of life of the Chinese general population (aged 55-64 years), the quality of life of septic patients were significantly lower at 3 months after discharge (p < 0.05). Comparing the quality of life of the ill patients who had been discharged at 3 mo and 24 mo, the general health improved statistically (p = 0.000) and clinically (score improvement > 5 points). Older age (OR, 1.050; 95% CI, 1.022-1.078, p = 0.000), female (OR, 3.375; 95% CI, 1.434-7.941, p = 0.005) and longer mechanical ventilation time (OR, 3.412; 95% CI, 1.413, 8.244, p = 0.006) were the risk factors for the quality of life of septic survivors.</p><p><b>CONCLUSION</b>The long-term quality of life of septic survivors was similar to that of non-sepsis critically ill survivors. After discharge, the general health of sepsis improved overtime. Age, female and mechanical ventilation time (>5 days) were the predictors of the quality of life after sepsis.</p>

Correlation between diabetic peripheral neuropathy and cardiovascular diseases in patients with type 2 diabetes mellitus / 心血管康复医学杂志

Objective :To explore correlation between diabetic peripheral neuropathy (DPN) and cardiovascular disea-ses (CVD) in patients with type 2 diabetes mellitus (T2DM).Methods :A total of 375 T2DM patients ,who were treated in our community health service center from Jan 2014 to Jul 2016 ,were selected .Demographic characteris-tics ,systolic blood pressure (SBP) ,blood lipids ,blood glucose ,electromyogram and CVD were collected in all sub-jects using questionnaire .According to complicated CVD or not ,patients were divided into CVD group (n＝54) and non-CVD group (n＝321).Correlation among all indexes and CVD risk were analyzed .Multifactor Logistic regres-sion analysis was used to analyze independent risk factors for CVD risk .Results :Among the 375 T2DM patients ,54 cases (14. 4%) were complicated with CVD .Compared with non-CVD group ,there were significant rise in age≥65 years ,abnormal fasting blood glucose (FBG) , abnormal 2h postprandial blood glucose (2hPG) , abnormal glycosy-lated hemoglobin A1c (HbA1c) and SBP in CVD group , P＜0.05 or ＜0.01 .Spearman correlation analysis indica-ted that age ,FBG ,2hPG ,DPN ,SBP and HbA1c were significant positively correlated with CVD risk (r＝0.612～0.735 , P＝0.001 all).Multifactor Logistic regression analysis indicated that DPN , abnormal FBG and abnormal 2hPG were independent risk factors for CVD (OR＝1.248～2.023 , P＜0.05 all).Conclusion : Diabetic peripheral neuropathy is one of the independent risk factors for CVD in T2DM patients .Attention should be paid to preven-tion ,screening and early treatment of CVD in these patients in clinic .

Clinical implication of minimal residue disease monitoring by WT1 gene detection and flow cytometry in myelodysplastic syndrome with allogeneic stem cell transplantation / 中华血液学杂志

Objective: To investigate the clinical significance of minimal residual disease (MRD) monitoring by using WT1 gene and flow cytometry (FCM) in patients with myelodysplastic syndrome (MDS) who receiving allogeneic stem cell transplantation (allo-HSCT). Methods: WT1 gene and MDS-related abnormal immunophenotype were examined by real-time quantitative polymerase chain reaction (RQ-PCR) and FCM, respectively. The bone marrow samples were collected from patients with MDS who received allo-HSCT from Feb, 2011 to Oct, 2015 in Peking University People's Hospital before and after transplantation. Results: Among 92 MDS patients, 40 (48.2%) patients were positive for WT1 (WT1(+)) and 9 (10.8%) patients were positive for flow cytometry (FCM(+)). 27 patients (29.3%) met the criteria of our combinative standard, MRDco (MRDco(+)). Only FCM(+) post-transplant (P<0.001) and MRDco(+) (P=0.017) were associated with relapse. The cumulative incidence of relapse (CIR) at 2 years were 66.7% and 1.2% (P<0.001) in FCM(+) and FCM(-) groups. MRDco(+) group had a 2-year CIR of 23.0% while MRDco(-) group had a 2-year CIR of 1.6% (P=0.004). The specificity of post-transplant WT1, FCM and MRDco to predict relapse was 59.0%, 96.4% and 74.7%, respectively. The sensitivity of these three MRD parameters to predict relapse was 66.7%. Conclusion: Post-transplant FCM and MRDco are useful tools to monitor MRD for MDS after transplantation. The preemptive intervention based on MRDco is able to reduce the relapse rate.

Distribution patterns of the contents of five biologically activate ingredients in the root of Scutellaria baicalensis / 中国天然药物

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.