Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, event-free survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.     

Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease

Objective

To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice models with Alzheimer disease (AD), and to explore the possible protective mechanism of acupuncture on mitochondria.

Methods

Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group, an acupuncture at non-acupoint group and a model group, 20 mice in each group. The 20 male senescence-accelerated mouse/resistance 1 (SAMR1) mice of the same age were used as a normal control group. Shenshu (BL 23), Baihui (GV 20), Xuehai (SP 10) and Geshu (BL 17) were selected for acupuncture intervention in acupuncture at acupoint group. After an 8-week intervention, mitochondrial tissues were extracted from the hippocampus. Differentially expressed proteins were identified by subcellular organelle proteomics. Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.

Results

Compared with the model group, there were 13 differentially expressed protein spots in the acupuncture at acupoint group, of which, 9 were up-regulated, including neurofilament light polypeptide (NFL), actin (cytoplasmic 1, database ID: ACTB), tubulin beta-2A chain (TBB2A), tropomodulin-2 (TMOD2), pyruvate dehydrogenase E1 component subunit beta (PDHE1-β), NADH-ubiquinone oxidoreductase 75 kDa subunit (database ID: NDUS1), heat shock cognate 71 kDa protein (HSC71), pyruvate dehydrogenase E1 component subunit alpha (PDHE1-α) and ATP synthase beta subunit (ATP-β); 4 were down-regulated, including glial fibrillary acidic protein (GFAP), pyruvate dehydrogenase phosphatase 1 (PDP1), mitochondrial-processing peptidase subunit alpha (MMP-α) and adenosine kinase (ADK). According to the information provided in the protein database, most of the differentially expressed proteins involve the regulation of mitochondrial function and structure. The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group (P<0.05). ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group (P<0.05); there was no significant difference between the acupuncture at non-acupoint group and the model group (P>0.05).

Conclusion

Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.

     

Academic ideas of Chinese medicine master HE Pu-ren

Prof.HE Pu-ren,also known as HE Shi-niu or HE Kong-shui,was born in Shigui Village,Laishui County,Hebei Province on May 20,1926.He was ambitious and present particularly smart and obsession with reading ever since childhood.     

Treatment of Infantile Muscular Torticollis with Tuina： A Report of 22 Cases

以推、揉、拿、扳、拉等手法,治疗22例肌性斜颈患儿,治愈18例,显效3例,无效1例.总有效率95.4%.     

Effects of acupuncture plus mild hypothermia on apoptosis-related factors in rats with cerebral ischemia-reperfusion

Objective

To investigate the effect of acupuncture plus mild hypothermia on neurological function impairment score, cerebral infarct size and apoptosis-related factors in cerebral ischemia reperfusion injury (CIRI) rats.

Methods

Sixty healthy male Sprague-Dawley (SD) rats were routinely reared for 1 week. Ten rats were randomly selected as the sham operation group and 10 rats as the blank control group, while the remaining 40 rats were subjected to preparing the middle cerebral artery occlusion (MCAO) model by modified filament occlusion method. The 40 MCAO rats were further randomly divided into a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group, with 10 rats in each group. Rats in the sham operation group, the blank control group and the model group did not accept treatment except binding; rats in the acupuncture group received acupuncture treatment; rats in the mild hypothermia group received mild hypothermia treatment; rats in the acupuncture plus mild hypothermia group received acupuncture and mild hypothermia treatment. 72 h after the treatment, neurological function impairment score was performed; the infarct area ratio was determined by 2,3,5-tripheyl tetrazolium chloride (TTC) staining; apoptosis of brain cells was observed by TUNEL method; the expressions of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry.

Results

Compared with the blank control group and the sham operation group, the neurological function impairment score, cerebral infarct area ratio, apoptosis, and the expressions of Bax and Caspase-3 in the model group were significantly increased, while the expression of Bcl-2 was significantly decreased, and there were significant between-group differences (all P<0.05). After the treatment, there were statistically significant differences among the treatment groups in the neurological function impairment score, cerebral infarct area ratio and apoptosis in the ischemic side of rats, as well as the expressions of Bcl-2, Bax and Caspase-3 (all P<0.05), and from the figures, tables and statistical analysis, it was found that a better tendency in the acupuncture plus mild hypothermia group than the acupuncture group or mild hypothermia group.

Conclusion

Acupuncture plus mild hypothermia can protect the brain cells by improving neurological function impairment, decreasing cerebral infarct area ratio, reducing the number of apoptotic cells in the ischemic area and regulating the expressions of apoptosis related proteins to inhibit apoptosis.

     

Effect of electroacupuncture and herbal cake-partitioned moxibustion on anxiety and depression in patients with crohn’s disease in remission

Objective

To observe the effect of electroacupuncture (EA) and herbal cake-partitioned moxibustion on anxiety and depression in patients with Crohn’s disease (CD) in remission.

Methods

Sixty CD cases were randomly allocated into an EA group (n=30) and an herbal cake-partitioned moxibustion group (n=30) using the random number table by the ratio of 1:1. In addition, 30 healthy subjects were included in a control group. Bilateral Tianshu (ST 25), Qihai (CV 6) and Zhongwan (CV 12) were used in the EA and herbal cakepartitioned moxibustion groups. The treatment was done 3 times a week, for a total of 12 weeks. The efficacy was evaluated using self-rating anxiety scale (SAS), self-rating depression scale (SDS) and traditional Chinese medicine (TCM) symptom scores.

Results

Before treatment, the SAS and SDS scores in CD patients were remarkably higher than those in healthy subjects. After EA or herbal cake-partitioned moxibustion treatment, the SAS and SDS scores were significantly decreased in both groups, showing significant intra-group differences (P<0.05); the symptom scores of abdominal pain (severity, frequency and duration), bowel sounds/flatus and general fatigue were significantly decreased, showing significant intra-group differences (P<0.05); however, there were no between-group statistical differences (P>0.05).

Conclusion

Both EA and herbal cake-partitioned moxibustion can significantly decrease abnormally high SAS and SDS scores in CD patients as well as TCM symptom scores. The two therapies share similar effects in alleviating common symptoms and improving anxiety and depression.

     

Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin

Colistin is often the only effective antibiotic against the respiratory infections caused by multidrug-resistant Gram-negative bacteria. However, colistin-resistant multidrug-resistant isolates have been increasingly reported and combination therapy is preferred to combat resistance. In this study, five combination formulations containing colistin (COL) and rifampicin (RIF) were prepared by spray drying. The lowest minimum inhibitory concentration (MIC) value against Pseudomonas aeruginosa PAO1 was measured for the formulation of COL/RIF?=?4:1 with relatively high emitted doses (over 80%) and satisfactory fine particle fractions (over 60%). Data from X-ray photoelectron spectroscopy (XPS) and nano-time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surfaces of particles were mainly covered by rifampicin even for the formulation with a mass ratio of COL/RIF?=?4:1. Because colistin is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither affected aerosolisation nor retarded dissolution rate of colistin in the combination formulations. For the first time, advanced surface characterisation techniques of XPS and ToF-SIMS have shown their capability to understand the effect of surface composition on the aerosolisation and dissolution of combination powders.     

The effects of daidzin and its aglycon,daidzein, on the scopolamineinduced memory impairment in male mice

In this study, the effect of daidzin or daidzein isolated from Pueraria lobata on the memory impairments induced by scopolamine was assessed in male mice using the passive avoidance and the Morris water maze tasks. Administration of daidzin (5 mg/kg) or daidzein (5 mg/kg) significantly reversed the scopolamine (1 mg/kg)-induced cognitive impairments in male mice as evidenced by the passive avoidance test (p < 0.05) and on the Morris water maze test (p < 0.05). Moreover, the ameliorating effects of daidzin or daidzein were antagonized by tamoxifen (1 mg/kg), the nonspecific estrogen receptor antagonist. These results indicate that daidzin or daidzein may be useful in cognitive impairment induced by cholinergic dysfunction, and this beneficial effect is mediated, in part, via estrogen receptor.     

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵mm³) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵mm³) with differences in volumes (p = .0055).     

A potential inhibitor of rat aortic vascular smooth muscle cell proliferation from the pollen of <Emphasis Type="Italic">Typha angustata</Emphasis>

By various chromatographic methods, three flavonoids, (2S)-naringenin (1), isorhamnetin 3-O-(2-O-α-l-rhamnopyranosyl) β-d-glucopyranoside (2), typhaneoside (3), and two sterol glycosides, β-sitosterol-3-O-(6-octadecanoyl) β-d-glucopyranoside (4) and β-sitosterol-3-O-(6-octadeca-9Z,12Z-dienoyl) β-d-glucopyranoside (5), were isolated from the pollen of Typha angustata. Their structures were determined on the basis of spectroscopic analyses. The flavonoids (1–3) were evaluated for their effects on the viability and proliferation of rat aortic smooth muscle cells. (2S)-naringenin (1) significantly inhibited cell proliferation in a dose-dependent manner without cytotoxic at concentrations of 30, and 50 μM; it reduced the number of cells following PDGF-BB treatment to 1.83 ± 0.30 × 10⁴ and 2.20 ± 0.60 × 10⁴ cells/well, respectively. These findings suggest that (2S)-naringenin has antiproliferative effects on aortic smooth muscle cells.