[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Predictive value of aMAP risk score for early recurrence of small hepatocellular carcinoma after microwave ablation].

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

[Research progress in radiomics based on CT and MRI images for prediction of microvascular invasion in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Microvascular invasion (MVI) is considered the major risk factor for postoperative recurrence and metastasis in HCC. The diagnosis of MVI relies on the postoperative pathological assessment of the tumor tissues. Seeking non-invasive methods and biomarkers for evaluation of MVI before surgery has important clinical implications for guiding surgical treatment and improving patients' survival. Recent studies have reported the applications of radiomics technique in prediction of MVI in HCC and showed promising results. Herein we summarized the research progress in CT- or MRI-based radiomics models for prediction of MVI in HCC to provide helpful thinking for further research in this field.

[Application of liquid biopsy in early screening and recurrence prediction of hepatocellular carcinoma].

The incidence and mortality of HCC in China account for approximately 50% of all cases worldwide. Low early diagnosis rate and high postoperative recurrence rate are two major causes for poor 5-year survival rate of HCC patients in China. At present, multiple problems such as low performance and compliance of screening technology and lack of effective markers for predicting postoperative recurrence, remain to be resolved. Due to the simplicity and accuracy, new molecular markers, such as liquid biopsy, are expected to serve as supplementary tools to traditional screening and early warning approaches, thereby realizing early detection and accurate treatment of HCC. In this article, research progress upon the clinical application of liquid biopsy in early screening and prediction of postoperative recurrence of HCC was reviewed, and prospects the future research.

[A survey of fluid therapy in 2 intensive care units].

To explore the present status of fluid therapy and clinical outcome in critically ill patients in intensive care units (ICU). ICU patients consecutively admitted to our ICU were prospectively enrolled. Patients' demographics, laboratory data, fluid record and clinical outcome were collected. Fluid intake quantity of all patients was at peak on the fifth day which was 2 806 (1 997, 3 582) ml. From the fourth day in ICU, fluid balance started to benegative as -84 (-1 127, 612) ml and gradually increased. Crystalloid solution was the main components. For treatment purposes, medication injections and nutrients were major fluids. Positive correlations were found between total fluid intake quantity, total crystalloid volume, total colloidal volume and hospital stay, ICU stay, duration of intubation (r values as 0.211, 0.686, 0.282, 0.155, 0.506, 0.174, 0.209, 0.072, 0.292, respectively P<0.05). Moreover, positive correlations were also demonstrated between total colloidal volume and total bilirubin, direct bilirubin, alanine transaminase, aspartate transaminase, blood urea nitrogen, serum creatinine (r values as 0.196, 0.242, 0.190, 0.335, 0.284, 0.223, respectively P<0.05).

[The diagnostic value of neuron-specific enolase, central nervous system specific protein and interleukin-6 in sepsis-associated encephalopathy].

Objective: To investigate the diagnostic value of neuron-specific enolase(NSE), central nervous system specific protein(S100ß), interleukin-6(IL-6) in sepsis-associated encephalopathy(SAE). Methods: Clinical data of patients admitted to ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in Xiangya Hospital, Central South University. SAE was defined as cerebral dysfunction in the presence of sepsis that also fulfilled the exclusion criteria. The acute physiology and chronic health score (APACHE Ⅱ), sequential organ failure assessment (SOFA), NSE, S100ß, IL-6, ICU stay time and 28-day mortality were compared between the two groups. NSE, S100ß and IL-6 were measured on the 1st and 3rd day in ICU to determine the optimal cut-off value of SAE. Results: Among 59 enrolled patients, 36 were assigned to SAE group while 23 were non-SAE group. The SAE group had a significantly higher APACHE Ⅱ and SOFA scores, as well as the length of ICU stay (P<0.01). The levels of NSE, S100ß and IL-6 in the two groups both increased on the 1st day, and decreased on the 3rd day. The level of NSE on the 1st day[19.28(13.00, 30.52) µg/L vs 16.61(7.58, 22.01 µg/L)] and the 3rd day[16.03(9.40, 21.29) µg/L vs 11.39(8.49, 15.00) µg/L, P=0.029], IL-6 on the 1st day[676.25(81.34, 5 000.00) mg/L vs [209.10(42.27, 648.20) mg/L, P=0.005] and the 3rd day[157.10(72.85, 687.63) mg/L vs 55.92(31.62, 177.00) mg/L, P=0.026] of SAE group was significantly higher than those of non-SAE group. However S100ß between groups on the 1st day [0.33(0.15, 0.54) µg/L vs 0.23(0.16, 0.53) µg/L] and the 3rd day[0.19(0.10, 0.29) µg/L vs 0.10(0.05, 0.17) µg/L] was neither significant (P>0.05). The diagnostic values for SAE of NSE, S100ß and IL-6 were 14.36 µg/L, 0.14 µg/L and 91.305 mg/L with sensitivity 61.1%, 61.1%, 72.2% and specificity 73.9%, 69.6%, 69.6%, respectively. The diagnostic AUC of NSE and IL-6 combination was 0.774, 95%CI 0.651-0.896. Conclusion: All sepsis patients have different degrees of brain injury. NSE combined with IL-6 on the 3rd day in ICU demonstrates the diagnostic significance of SAE.

[Effect of neuroglobin on oxygen-glucose deprivation and reoxygenation induced autophagy in a human neuroblastoma cell line].

Objective: To investigate the effect of neuroglobin on oxygen-glucose deprivation and reoxygenation (OGD/R) induced autophagy in a human neuroblastoma cell line (SH-SY5Y). Methods: SH-SY5Y cells were transfected with plasmids (or vector) to establish a stable cell line of NGB overexpression (OE). After treated with OGD/R, cells were collected for the analyses of mRNA (Atg5, Atg7, BECN1 and FUNDC1) and protein levels of LC3. Furthermore, mitochondrial and cytosolic fractions were isolated for protein levels of PINK1 and Parkin. Results: Treatment of OGD/R significantly increased the levels of mRNA of Atg5, Atg7, BECN1 and FUNDC1 (peak levels were 4.90±0.71, 6.72±0.75, 2.71±0.39 and 3.96±0.78 fold, all P<0.05). The protein level of Parkin increased in mitochondria and decreased in cytoplasm after the treatment. Compared with the vector group, Ngb OE group showed a significant higher level of FUNDC1 mRNA (3.96±0.78 versus 6.86±0.63 fold, P<0.05), while Atg5, Atg7 and BECN1 mRNA levels showed no significant difference. Moreover, the mitochondrial or cytosolic protein levels of PINK1 or Parkin showed no significant difference between Ngb OE and vector group. Conclusions: Overexpression of Ngb can not affect autophagy or mitohpagy in OGD/R treated SH-SY5Y cells. Overexpression of Ngb can increase the mRNA level of FUNDC1 and the mechanism needs further study.

Upregulated serum sclerostin level in the T2DM patients with femur fracture inhibits the expression of bone formation/remodeling-associated biomarkers via antagonizing Wnt signaling.

OBJECTIVE: Bone formation/remodeling-associated biomarkers, such as osteocalcin, amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the osteoblast activity and downregulates the bone turnover. PATIENTS AND METHODS: In the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP and CTX in the T2DM patients. We evaluated the regulation on osteocalcin, P1NP and CTX by sclerostin treatment in osteoblast hFOB 1.19 cells. Finally, we determined the mediation of Wnt signaling in the regulation by sclerostin on osteocalcin, P1NP and CTX in human osteoblast hFOB 1.19 cells. RESULTS: It was demonstrated that osteocalcin, P1NP and CTX were downregulated in the femur fracture of patients with T2DM, whereas the serum level of the sclerostin was markedly higher in the femur fracture of patients with T2DM. Moreover, the downregulated osteocalcin, P1NP or CTX was negatively associated with the upregulated sclerostin. In vitro results confirmed that sclerostin downregulated the expression of osteocalcin, P1NP and CTX in hFOB 1.19 cells. Also, our results demonstrated that Wnt/ß-catenin inhibition was associated with the sclerostin-mediated inhibition of osteocalcin, P1NP and CTX in hFOB 1.19 cells. The Wnt/ß-catenin level was markedly inhibited by sclerostin treatment, and the siRNA-mediated downregulation of ß-catenin reduced the levels of osteocalcin, P1NP and CTX. CONCLUSIONS: Our study demonstrated that the upregulated serum sclerostin level in the T2DM patients with fracture inhibited the expression of the bone formation/remodeling-associated biomarkers via antagonizing Wnt signaling. It suggests that sclerostin might be an effective target for T2DM-associated bone fracture and delayed fracture healing.

[Clinical characteristics and therapeutic effect of drug-resistant tuberculosis in children].

Objective: To explore the clinical characteristics of drug-resistant tuberculosis (TB) in children and to study the effectiveness of second-line anti-TB therapy for children and to examine the incidence of adverse drug reactions. Method: Retrospective research was conducted. The clinical records of children in West China Second Hospital diagnosed as drug-resistant TB from January 2010 to June 2014 were investigated.The clinical characteristics and risk factors were analyzed retrospectively. Treatment effect at discharge was examined as a short-term outcome indicator to evaluate the effectiveness of second-line anti-TB therapy and the incidence of adverse drug reactions. χ(2) test was used. Result: Forty-six patients were diagnosed as drug-resistant TB in 443 children infected with TB, with a 10.4% resistance rate. The 46 children included 26 male and 20 female patients, aged from one month and 28 days to 17 years and 5 months, with the average age (8.4±4.5) years, >7 to 14 years old patients as the biggest part(25 patients, 54.3%). Among the 46 children, 20 patients(43.5%)had close contact with TB patients, of whom 12 patients (60.0%) contacted with family members (including parents, brothers and sisters and grandparents living together) and 8 patients(40.0%) contacted with patients from outside family (such as relatives or neighbors). Moreover, 11 cases (23.9%) were under initial treatment and 35 cases (76.1%) were retreated.From 2010 to 2014, the number of cases of initial and retreated patients had no significant difference(0 and 1, 1 and 13, 4 and 7, 4 and 11, 2 and 3 cases, χ(2)=3.255, P=0.196). Among retreated patients, 31.4% (11/35) had irregular treatment before.Until discharge, the effective rate was 87.0% (40/46), while the incidence rate of adverse drug reaction was 10.9%(5/46). Conclusion: The therapy for drug-resistant TB is effective and the incidence of adverse drug reaction is relatively low.

[The role of neuroglobin in oxygen-glucose deprivation and reoxygenation-induced mitochondrial depolarization and reactive oxygen species production in SH-SY5Y cells].

Objective: To investigate the role of neuroglobin (NGB) in oxygen-glucose deprivation and reoxygenation (OGD/R) induced mitochondrial depolarization and reactive oxygen species (ROS)production in a human neuroblastoma cell line (SH-SY5Y). Methods: SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown (KD). After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels. Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope. Also, to determine the neurotoxicity, we measured the lactate dehydrogenase(LDH)level in the cell culture medium. Results: After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04±0.35 fold, 1.69±0.18 fold). Compared with the vector group, NGB KD group had much more mitochondrial depolarization [JC-1 red/green (1.10±0.10) vs (1.46±0.11), P<0.05] and ROS production [DCFH-DA fluorescence (36.30±5.32) vs (16.26±2.97), P<0.05]. Furthermore, NGB KD groups had a higher level of LDH release [(63.42±6.14)%vs (49.65±5.09)%, P<0.05]. Conclusions: NGB plays an important role in the homeostasis of mitochondria. Knockdown of NGB results in increased mitochondrial depolarization, ROS production and neurotoxicity under hypoxia circumstances.

[Influences of DNA methylation upon neuroglobin sustained expression in oxygen- glucose deprivation model].

Objective: To investigate the influences of genomic DNA methylation upon neuroglobin sustained expression in oxygen- glucose deprivation model. Methods: With A549 cell strain as the research object, the control group were cultivated in the complete medium containing 10 µmol/L of 5-azacytidine for 4 days, and the control group was cultivated in the complete medium for 4 days.Then carried out oxygen glucose deprivation treatment for 4 h.Detecting neuroglobin expression, DNA methyltransferase expression, cell inhibition ratio and DNA methylation level at different time points. Results: DNA methylation level of the experimental group declined apparently[6 h : (1.0±0.0) vs (2.1±0.3); 12 h: ( 0.9±0.0) vs (1.4±0.0); 24 h: (0.9±0.0) vs (2.6±0.2); 36 h: (0.9±0.0) vs (2.9±0.1)], neuroglobin expression of the experimental group continued and was obviously higher than that of the control group at the same time point[NGB-PCR: 6 h: (3.3±1.1) vs (0.4±0.1); 12 h: (3.2±0.8) vs (0.1±0.1); 24 h: (4.6±0.6) vs (0.2±0.0); 36 h : (5.1±0.3) vs (0.1±0.1)], while the Cell inhibition ratio of the experimental group was obviously lower than that of the control group at the same time point[(6 h: (10.4±0.5) vs (14.1±0.7); 12 h: (22.0±1.3) vs (35.1±0.5); 24 h: (25.7±1.0) vs (40.6±1.3); 36 h: (30.0±0.8) vs (44.4±0.7)], differences had statistical significance (P<0.05).mRNA expression of three methyltransferases of the experimental group was higher than that of the control group at different time points, where, DNMT1 and DNMT3B showed great differences (P<0.05), while differences in DNMT3A of two groups had no statistical significance (P>0.05). Conclusions: In the OGD/R model of A549 cell strain, genomic DNA methylation resulted in unsustained expression of neuroglobin, but neuroglobin expression increased after demethylation inhibitor was used.

Mechanisms of the relaxant effect of a danshen and gegen formulation on rat isolated cerebral basilar artery.

AIM OF THE STUDY: Danshen (root of Salvia miltiorrhiza) and gegen (root of Pueraria lobata) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, the actions of a danshen and gegen formulation (DG; ratio 7:3) were investigated on rat-isolated cerebral basilar artery. MATERIALS AND METHODS: Rat basilar artery rings were precontracted with 100 nM U46619. Involvement of endothelium-dependent mechanisms was investigated by mechanical removal of the endothelium; K(+) channels were investigated by pretreatment of the artery rings with various K(+) channel inhibitors, and Ca(2+) channels were investigated in artery rings incubated with Ca(2+)-free buffer and primed with 100 nM U46619 for 5 min prior to adding CaCl(2) to elicit contraction. RESULTS: DG produced concentration-dependent relaxation of the artery rings with an IC(50) of 895±121 µg/ml. Mechanical removal of the endothelium or pretreatment with the BK(Ca) channel inhibitor iberiotoxin (100 nM), the K(V) channel inhibitor 4-aminopyridine (1 mM), or the K(IR) channel inhibitor barium chloride (100 µM), all had no effect on the DG-induced response (P>0.05 for all). However, pretreatment with the K(ATP) channel inhibitor glibenclamide (1 µM), the non-selective K(+) channel inhibitor tetraethylammonium (TEA, 100 mM), or a combination of all the K(+) channel inhibitors (iberiotoxin+4-aminopyrindine+barium chloride+glibenclamide+TEA) produced significant inhibition on the DG-induced response (P<0.01 for all); its maximum vasorelaxant effect (Imax) was reduced by 37, 24, and 30%, respectively. Preincubation of the artery rings with DG for 10 min produced concentration-dependent (1, 3 and 7 mg/ml) and total inhibition on the CaCl(2)-induced vasoconstriction. CONCLUSIONS: These findings suggest the vasorelaxant effect of DG on rat basilar artery is independent of endothelium-derived mediators, whereas, inhibition of Ca(2+) influx in the vascular smooth muscle cells is important, and a minor component is mediated by the opening of K(ATP) channels. DG could be a useful cerebroprotective agent in some patients with occlusive cerebrovascular disease.

[Observation on left ventricular diastolic function of patients with heart-deficiency syndrome of cardiovascular diseases].

In this paper, left ventricular diastolic function (LVDF) of 99 Heart-Deficiency Syndrome (HDS) patients was observed with pulse Doppler echocardiogram and was compared with normal group. The results showed that different LVDF abnormalities occurred in the HDS patients. When E, Ei DC were decreased and A, Ai, A/E, Ai/Ei, IRT increased, the degree of HDS deteriorated, the pattern was Heart Qi-Yin Deficiency > Heart Yang Deficiency > Heart Qi Deficiency > Heart Yin Deficiency. In conclusion, the above parameters of LVDF could be important indices for evaluation of HDS.

Cytoarchitectural characteristic of the frontal eye fields in macaque monkeys.

The cytoarchitecture of the prearcuate gyrus, including the region of the physiologically defined frontal eye fields (FEF), was studied in four macaque monkeys (Macaca fascicularis, M. mulatta) to determine if the FEF could be anatomically identified. Brain sections were stained with standard Nissl and, in some cases, myelin stains. Two nonstandard planes of section were used: one tangential to the prearcuate gyrus and the second normal to the most posterior bend of the prearcuate gyrus. The first plane of section was advantageous for studying the location of the FEF with reference to the entire medial-lateral extent of the gyrus and the second allowed good comparisons of the FEF to adjacent anterior and posterior cortical areas. Frontal plane sections through the prearcuate gyrus were also examined in 15 macaque monkeys for comparison with sections cut normal to the posterior bend of the gyrus and tangential to the gyrus. Intracortical microstimulation was performed in three monkeys. The FEF was defined as the area from which low-threshold (less than or equal to 50 microA) saccades could be evoked. The area extended about 10 mm along the anterior bank of the arcuate sulcus. Within the area, saccade amplitudes were represented in a mediolateral, large-to-small topography. No topography of saccade direction was noted within FEF but reversals of saccade direction for any given electrode pass were found. These results confirm the results from our earlier mapping study of FEF (Bruce et al.: J. Neurophysiol. 54:714-734, '85). Cell bodies of large pyramidal cells in layers III and V of the prearcuate gyri from three hemispheres were measured with the aid of an image-combining computer microscope. The distribution of cells of greater than 22 microns diameter or cross-sectional areas of greater than 500 microns 2 were plotted. In one monkey, marker lesions made at microstimulation sites within the FEF or in adjacent non-FEF areas were also plotted. The location of the FEF appeared to coincide with the concentration of large layer V pyramidal cells in the prearcuate gyrus rather than with any previously mapped cytoarchitectonic area. The numbers of large pyramids in layer V were noticeably reduced along the lip of the prearcuate gyrus and at dorsomedial and ventrolateral locations which were outside the physiologically defined FEF.

The role of striate cortex in the guidance of eye movements in the monkey.

We studied the effect of unilateral striate cortical ablations on smooth pursuit and saccadic eye movements in the monkey. The monkeys made quite accurate saccades to stationary stimuli in the field contralateral to the lesion, and they readily pursued foveal targets moving in all directions. However, when visual stimuli were stepped into the field contralateral to the lesion and then began to move, thus insuring that the moving stimulus was confined to the impaired visual hemifield, several oculomotor abnormalities emerged. Saccades to moving stimuli presented in the impaired field consistently undershot targets that moved away from the central fixation point after the step, and overshot targets that moved back towards the central fixation point. There was little or no smooth pursuit eye velocity generated in any direction to moving stimuli in the impaired field, and the monkeys could not generate smooth pursuit to stimuli maintained a few degrees from the fovea in the impaired field, although they were able to pursue such stimuli held in the normal field. Ablation of striate cortex also affected the latencies of saccades. When step-ramp stimuli were presented in the normal field, the monkeys delayed the initiation of saccades to targets moving towards the central fixation point, and hastened the initiation of saccades to targets moving away from the central fixation point. By contrast, changes in the direction of target movement did not affect the latencies of saccades into the impaired field. The deficits seemed permanent, lasting as long as the monkeys were tested--over 2 years in one case--but they were not total. Each monkey could use stimuli moving into the affected field to develop some eye velocity, although this residual ability had a much longer latency and lower gain than that provided by the intact visual system. These results show that striate cortex is intimately involved in the estimation of stimulus velocity critical to the genesis of smooth pursuit and saccadic eye movements.