OBJECTIVEMonitoring of minimal residual disease (MRD) is proven to be increasingly valuable for predicting relapse and outcome of childhood acute lymphoblastic leukemia (ALL) and is used to identify patients' risk groups in several current clinical trials. However, the limitation is that most studies focused on the cut-off value at 10(-4) and the time point after induction. The aim of this study was to investigate the predictive values of different MRD levels detected at different chemotherapy phases in childhood ALL.

METHODSOne hundred and two patients were enrolled in this study from January 2002 to December 2004 in our hospital. All the patients were treated with modified National Protocol of Childhood ALL in China 1997. MRD levels were detected on the 15th day, 29th day, at 3 months, 6 months and 12 months after initial chemotherapy. All samples were stained with a panel of four colour combinations of fluorochrome conjugated monoclonal antibodies according to the leukemia-associated immunophenotype (LAIP) defined at diagnosis and analyzed by multi-parametric flow cytometry. CD45CD19CD34CD10, CD45CD19CD34CD20 and CD45CD19CD10CD20 were the most common combinations in B lineage ALL, while CD45CD2CD3CD7 and CD45CD2CD3CD34 were the most frequently used immunophenotypes for T lineage ALL. The median follow-up time was 63.3 months ranged from 40.6 to 87.5 months.

RESULTSOf the 102 patients, 64 were male and 38 were female, with a median age of 5.7 (0.2 - 14.8) years. Eighty-eight cases were diagnosed as B lineage ALL and the remaining 14 were T-ALL. The 5-year overall survival (OS) rate and event free survival (EFS) rate for this cohort were (86.9 +/- 3.4)% and (79.9 +/- 4.0)%, respectively. Twelve patients underwent relapse. Among the 102 patients, 14.3% had negative MRD (MRD < 10(-4)) on day 15, 43.9% on day 29, 39.1%, 39.7% and 45.6% had negative MRD at the third, sixth and twelfth month after chemotherapy. Patients who could achieve negative MRD within one year had superior outcome to the others [5-year EFS rates: (92.5 +/- 3.2)% vs. (58.3 +/- 8.6)%, P < 0.001]. The EFS for patients based on MRD levels measured at different stages of therapy were compared by Kaplan-Meier analyses. MRD was predictive of outcome at all 5 time points at a range of thresholds. The optimum threshold, selected for each time point on the basis of log rank analysis, progressively dropped from 10(-2) of day 15 [5-year EFS rates (79.8 +/- 10.3)% vs. (28.6 +/- 17.1)%, P < 0.001], to 10(-3) of day 29 [5-year EFS rates (88.3 +/- 4.9)% vs. (51.3 +/- 14.4)%, P < 0.003], to 10(-4) at 3 [5-year EFS rates (92.4 +/- 5.1)% vs. (65.5 +/- 7.5)%, P < 0.015], 6 [5-year EFS rates (96.3 +/- 3.6)% vs. (65.4 +/- 7.5)%, P < 0.003] and 12 [5-year EFS rates (100.0 +/- 0.0)% vs. (67.7 +/- 8.4)%, P < 0.002] months. And the hazard ratios for relapse and death at higher MRD level groups were 5.91 (95%CI: 1.9 - 18.9), 5.02 (95%CI: 1.5 - 16.5), 5.21 (95%CI: 1.2 - 22.9) and 11.10 (95%CI: 1.5 - 84.5) on day 15, day 29, at month 3 and month 6, respectively. And MRD >or= 10(-2) on day 15 was proven to be an independent predictor by multivariate Cox proportional-hazards regression model.

CONCLUSIONDynamic MRD detection by multi-parametric flow cytometry is highly predictive of outcome for childhood ALL, and the cut-off values at different time points were different.

Adolescent ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Infant ; Infant, Newborn ; Male ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; pathology ; Predictive Value of Tests ; Prognosis

OBJECTIVE: To investigate the efficacy of single oblique lumbar interbody fusion(OLIF) with robot-assisted posterior internal fixation for the treatment of lumbar degenerative diseases. METHODS: The clinical data of 67 patients with lumbar degenerative diseases treated from September 2019 to December 2020 was retrospectively analyzed. According to different surgical methods, the patients were divided into traditional group and robot group. The traditional group received traditional OLIF with posterior fluoroscopy percutaneous nail fixation, and the robot group received OLIF with robot-assisted posterior internal fixation. There were 33 patients in traditional group, including 13 males and 20 females, aged from 44 to 82 years old with an average of (59.7±9.1) years; and 34 cases in robot group, including 7 males and 27 females, aged from 45 to 81 years old with an average of(61.6±8.8) years. The operation time, fluoroscopy time, intraoperative blood loss, postoperative out of bed time and hospital stay were recorded. The visual analogue scale (VAS) of low back pain and Oswestry Disability Index(ODI) were compared before operation and 3 days, 3 months after operation between two groups. The accuracy of nail placement was evaluated by postoperative CT scan. RESULTS: Both groups of patients successfully completed the operation and were followed up for more than 3 months. The operation time, fluoroscopy time, intraoperative blood loss, postoperative out of bed time and hospital stay in traditional group were(299.85±15.79) min, (62.58±10.83) min, (118.33±10.80) ml, (2.5±0.7) d, (9.67±2.13) d;and robot group was(248.53±14.22) min, (19.47±3.51) min, (115.74±9.86) ml, (2.3±0.6) d, (9.44±1.93) d, respectively. The symptoms of postoperative low back pain, lower limb pain and numbness were significantly improved in all patients. The operation time and fluoroscopy time in robot group were significantly less than those of traditional group. There was no significant difference in intraoperative blood loss, postoperative out of bed time, hospital stay, VAS and ODI before and after operation (P>0.05). The accuracy of nail placement in robot group was 98.8% (2/160), which was higher than 89.9% (16/158) in traditional group. CONCLUSION Treatment of lumbar degenerative diseases with single body position OLIF with robot-assisted posterior minimally invasive internal fixation has less operation time and fluoroscopy time, high nail placement accuracy and accurate surgical effect, which is worthy to be popularized in clinic.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lumbar Vertebrae/surgery* ; Lumbosacral Region ; Male ; Middle Aged ; Retrospective Studies ; Robotics ; Spinal Fusion/methods* ; Treatment Outcome

OBJECTIVETo illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.

METHODThe BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.

RESULTThe primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.

CONCLUSIONThe significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Sensitivity and Specificity ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEAcute promyelocytic leukemia (APL) is a specific type of hematopoietic malignancy, accounting for 10% of the de novo acute myeloid leukemia (AML). The data on long-term outcome of APL in children are limited. The aim of this study was to investigate the clinical biological features, diagnosis, prognosis and long-term survival of childhood APL.

METHODSA total of 46 children with newly diagnosed APL from April 1998 to October 2005 were enrolled into this study. Induction treatment containing all-trans retinoic acid (ATRA) plus daunorubicin (DNR) or pirarubicin (THP) was performed on these patients, followed by 6 courses of chemotherapy consolidation: DNR, homoharringtonine or etoposide plus Ara-C. A maintenance therapy was then administered once 3-6 months. The total period of treatment was 2.5 years.

RESULTSOf the 39 patients who had completed the regular treatment, 36 (92.3%) achieved a complete remission. The 5-year cumulative incidence of relapse (CIR) was 28.6%. The estimated overall survival (OS) rates at 1, 3 and 5 years were (86.1 +/- 5.8)%, (76.1 +/- 7.5)% and (70.2 +/- 8.9)% respectively, while the event free survival (EFS) rates were (78.4 +/- 6.8)%, (63.6 +/- 8.7)% and (53.1 +/- 10.0)% respectively. The 5-year OS rate of patients with WBC less than or equal to 10.0 X 10(9)/L was (81.4 +/- 10.3)%, which was significantly higher than that with WBC greater than 10.0 X 10(9)/L[(51.6 +/- 14.7)%, P < 0.05]. Five patients with RT-PCR positive for PML/RARalpha S (short) subtype died eventually although all of them achieved CR, but none of the 13 patients with PML/RARalpha L (long) subtype died.

CONCLUSIONSRemission induction therapy with ATRA + DNR or THP is effective and safe for newly diagnosed childhood APL. The remission induction therapy combined with chemotherapy containing high/intermediate dose Ara-C can improve the long-term survival rates of APL patients. High WBC count and S subtype of PML-RARa are two poor prognostic factors for children with APL.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Oncogene Proteins, Fusion ; genetics ; Prognosis ; Survival Rate ; Treatment Outcome ; Tretinoin ; administration & dosage

ObjectiveTo compare the effects and differences of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics. MethodsTwenty-four male SD rats were randomly divided into sham-surgery， model， traditional Chinese medicine （TCM）， and ator-vastatin groups， with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water， TCM group received Yiqi Liangxue Shengji Formula 6 g/（kg·d）， and the atorvastatin group treated with atorvastatin suspension 2 mg/（kg·d） for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta； ELISA detection was used to test serum nitric oxide （NO） and C-reactive protein （CRP） levels； UPLC MS/MS technology was used for widely targeted metabolomics detection in serum， and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs； finally， compare serum levels of key metabolic markers of the above two medications in rats of each group. ResultsCompared with the sham-surgery group， the neointima significantly thickened， the level of NO decreased significantly and the level of CRP increased in serum of the model group （P＜0.01）； compared with the model group， the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced， with an increase in NO levels and a decrease in CRP levels （P＜ 0.05 or P＜0.01）. The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways， while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine （16∶1/0∶0） ［LPC （16∶1/ 0∶0）］， phosphatidylcholine （15∶0/15∶0） ［PC （15∶0/15∶0）］ were the key metabolites of glycerophospholipid metabolic pathway； ornithine， spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of Yiqi Liangxue Shengji Formula. Compared with the sham-surgery group， LPC （16∶1/0∶0）， ornithine， and spermidine levels elevated and PC （15∶0/15∶0） levels decreased in the model group （P＜0.05 or P＜0.01）. Compared with the model group， LPC （16∶1/0∶0）， ornithine， and spermidine levels decreased， and PC （15∶0/15∶0） levels increased in both TCM group and atorvastatin group （P＜0.05 or P＜0.01）. The degree of LPC reduction （16∶1/0∶0） was more significant in atorvastatin group compared with that in the TCM group （P＜0.01）. ConclusionsBoth sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism， exert the characteristics of lipid-lowering， anti-inflammatory， improve arginine/NO bioavailability， and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory， while Yiqi Liangxue Shengji Formula has unique characteristics in regulating energy metabolism and improving oxidative stress.

Background: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients’ kidney function recovery. Methods: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients’ renal function recovery at discharge, fluid balance, and levels of CVP were assessed. Results: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ² = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ² = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. Conclusion Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

In this paper, based on the supramolecular "Qi chromatography" of traditional Chinese medicine (TCM), combined with the characteristics of corona virus disease 2019 (COVID-19), the historical origin and characteristics of theoretical research on the treatment of epidemic diseases by TCM were analyzed retrospectively, and the key scientific problems for achieving its modernization were proposed, and the countermeasures were illustrated. In fact, the emergence and development history of TCM epidemic theory is a comprehensive and scientific understanding of biomolecular chemistry for epidemic caused by pathogen. From the exploration of the cause of abnormal Qi to the epidemic pathogenic factor, from the treatment based on syndrome differentiation by six meridians to by the defensive Qi and nutrient blood and the triple energizer, which is gradually close to the modern theoretical system of infectious diseases and immunology, all of which are stamped with brand of TCM supramolecular "Qi chromatography" theory. In the long history of biological evolution in nature, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as epidemic pathogenic factor in TCM, human body and Chinese materia medica are biological supramolecules at a specific stage of evolution in nature, which are controlled by the "imprinting templates" of molecular society in gradual biomolecules, with the unchanged laws of mutual advancement, mutation, suitability and mutual restriction. Based on the analysis of the law of supramolecular action hiding in the prevention and treatment of epidemic diseases dealt with TCM on procession of principle-method-recipe-medicines, this paper discusses the key scientific problems of its modernization and puts forward the solutions. It can not only clarify the scientific principle of the prevention and treatment with TCM, develop the multi-component Chinese medicine, accelerate the control of the epidemic situation, but also promote the solution of original frontier key scientific problems such as the material basis of meridians, viscera and syndromes, and the compatibility law of the TCM prescription, in order to protect the existing medical resources and open up a new situation in the modernization of TCM research.