Spinal Cord Stimulation Alleviates Pain Hypersensitivity by Attenuating Neuroinflammation in a Model of Painful Diabetic Neuropathy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is an intractable chronic pain condition affecting a growing number of adults in China. Spinal cord stimulation (SCS) has been employed in the treatment of PDN for several decades. However, the efficacy and underlying mechanisms of SCS are still inconclusive. METHODS: In this study, we adopted an implantable pulse generator to deliver electrical stimulation (50 Hz, 200 us pulse width, 12 hours/day in 5 weeks) via a quadripolar electrode in the lumbar epidural space to treat pain hypersensitivity in the rat model of PDN. Electronic von Frey and Hargreaves tests were used to measure the responses to mechanical and heat stimuli, respectively. Quantitative PCR, western blotting, and enzyme-linked immunosorbent assay (ELISA) were adopted to explore the changes in neuroinflammation after SCS. RESULTS: SCS alleviated mechanical allodynia and heat hyperalgesia over a period of 3 weeks in diabetic rats. SCS completely suppressed neuropathy-induced Tlr4 and NFκB p65 elevation, resulting in the reduction of pain-promoting Il1ß, Il6, and Tnfα proteins in the spinal cord dorsal horn. CONCLUSIONS: SCS may alleviate diabetic neuropathy-induced pain hypersensitivity via attenuating neuroinflammation in the spinal cord dorsal horn.

Canagliflozin alleviates high glucose-induced peritoneal fibrosis via HIF-1α inhibition.

The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin in vitro by simulating hypoxia with CoCl2 in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl2 hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-ß/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-ß/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-ß/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-ß/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-ß/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report.

BACKGROUND: Intestinal natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive non-Hodgkin's lymphoma, and its occurrence is closely related to Epstein-Barr virus infection. In addition, the clinical symptoms of NKTCL are not obvious, and the specific pathogenesis is still uncertain. While NKTCL may occur in any segment of the intestinal tract, its distinct location in the periampullary region, which leads clinicians to consider mimics of a pancreatic head mass, should also be addressed. Therefore, there remain huge challenges in the diagnosis and treatment of intestinal NKTCL. CASE SUMMARY: In this case, we introduce a male who presented to the clinic with edema of both lower limbs, accompanied by diarrhea, and abdominal pain. Endoscopic ultrasound (EUS) showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas. Under the guidance of EUS- fine needle biopsy (FNB) with 19 gauge or 22 gauge needles, combined with multicolor flow cytometry immunophenotyping (MFCI) helped us diagnose NKTCL. During treatments, the patient was prescribed the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy regimen. Unfortunately, he died of leukopenia and severe septic shock in a local hospital. CONCLUSION: Clinicians should enhance their understanding of NKTCL. Some key factors, including EUS characteristics, the right choice of FNB needle, and combination with MFCI, are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways.

Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 µg/mL) and capsaicin (25, 50, 75, or 100 µg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 µg/mL, tumor necrosis factor (TNF)-α level was 860 µg/mL, and nitric oxide (NO) level was 19.8 µg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.

Translation and validation of the Chinese version of the orthorexia nervosa assessment questionnaires among college students.

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).

Immunomodulatory Effects of Sinensetin on Macrophage and Cyclophosphamide-induced Immunosuppression in Mice.

In this study, we investigated the immunomodulatory effects of sinensetin (SI) on RAW 264.7 macrophages and cyclophosphamide (CY)-induced immunosuppressed mice. The results showed that SI enhanced macrophage activity and promoted the secretion of NO, IL-1ß, and TNF-α in vitro. Compared with the CY-induced immunosuppressed mice, in mice treated with SI, the body weights, organ indices, and total lymphocytes increased. Furthermore, SI promoted the secretion and mRNA expression of IFN-γ, IL-2, and IL-6 and reduced the damage caused by CY to the organs of the immune system. Moreover, it increased the activities of GSH-Px, CAT, SOD, and T-AOC and decreased the level of MDA. This study suggests that SI has the potential to be used as an immunity enhancer in the functional food and healthcare industries.

Vitexin-2-O-rhamnoside improves immunosuppression, oxidative stress, and phosphorylation of PI3K/Akt signal pathway in cyclophosphamide treated mice.

Vitexin-2-O-rhamnoside (VR) is an important active substance in hawthorn, which is widely used as a food or functional food raw material; however, its immunomodulatory activities have not been extensively studied. In this study, BALB/c mice immunocompromised by cyclophosphamide (CY) were used as models to explore the effects of VR on the immunity and antioxidant capacity of mice. The results revealed that VR can restore weight to the immunosuppressed mice to varying degrees, improve spleen and thymus injury, and restore peripheral blood levels. Furthermore, it can effectively promote the proliferation of T and B lymphocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) cell activities, and the secretion and mRNA expression of cytokines IFN-γ, IL-2, IL-6, and IL-12 to 0.36, 0.34, 50.25%, 45.74%, 28.36 pg/mL or 0.68, 31.81 pg/mL or 0.74, 20.40 pg/mL or 0.75, and 19.81 pg/mL or 0.55, respectively. Moreover, it can upregulate the phosphorylation level of PI3K/Akt signaling pathway in mice immunosuppressed by CY, increase the activities of glutathione peroxidase (GSH-Px), chloramphenicol acetyltransferase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and decrease the level of malondialdehyde (MDA). This study provides a theoretical and experimental basis for the research and development of health products with targeted efficacy, and the development of diversified products in the hawthorn deep-processing industry.

Effect of Photoperiod on Longevity, Food Consumption, and Reproduction of Holotrichia oblita (Coleoptera: Scarabaeidae).

Holotrichia oblita (Faldermann) (Coleoptera: Scarabaeidae) is a major soil insect pest that damages forest trees, crops, and lawns. Adults of H. oblita fly, forage, and mate at night but remain underground during the day. We studied the effect of photoperiod on H. oblita reproduction. H. oblita females laid more eggs at 8:16 (L:D) h and 0:24 (L:D) h than other photoperiods. As the scotophase increased, the preoviposition period decreased and the oviposition period increased. Female longevity exceeded that of males at all photoperiods, and both males and females at 0:24 (L:D) h had the shortest longevity. The number of eggs laid per female increased with increasing food consumption. Females at 8:16 (L:D) h had the greatest food consumption and laid the most eggs, while females at 24:0 (L:D) h had the lowest food consumption and laid few eggs. The food intake of adults increased gradually and decreased slowly after reaching a peak. Females began to lay eggs when their food consumption reached a maximum. These results indicate that a scotophase is necessary for the reproduction of H. oblita. A long scotophase promotes greater oviposition. The effect of photoperiod on reproduction is affected by food intake.

Permeability characteristics and structural evolution of compacted loess under different dry densities and wetting-drying cycles.

Permeability characteristics of compacted loess is always an important topic in soil mechanics and geotechnical engineering. This study explored the permeability characteristics of compacted loess under different dry densities and wetting-drying cycles, and found that as the dry density increases, the compacted loess surface became denser, the saturation permeability coefficient and saturation infiltration rate decreased. However, the wetting-drying cycle presented the opposite result. Meanwhile, the evolution of the microstructure was investigated by Scanning Electron Microscope (SEM) and Nuclear Magnetic Resonance (NMR) to explain the change of its permeability characteristics. The size of compacted loess aggregates was quantitatively analyzed by Image-Pro Plus (IPP) software. It showed that the size of compacted loess aggregates for different dry densities were concentrated from 10-100 µm, occupying 65.0%, 58.19%, and 51.64% of the total aggregates area respectively. And the interesting finding was that the area occupied by 10-50 µm aggregates remained basically unchanged with the number of wetting-drying cycles increasing. Therefore, the size of 10-50 µm aggregates represented the transition zone of compacted loess. NMR analyses revealed that with increasing dry density, the volume of macropores in the compacted loess rapidly decreased, the volume of mesopores and small pores increased. Meanwhile, the change in micropores was relatively small. The pore volume of the compacted loess after three wetting-drying cycles increased by 8.56%, 8.61%, and 6.15%, respectively. The proportion of macropores in the total pore volume shows the most drastic change. Variations in aggregate size and connection relationships made it easier to form overhead structures between aggregates, and the increased of macropore volume will form more water channels. Therefore, the change in permeability characteristics of compacted loess is determined by aggregate size, loess surface morphology, and the total pore volume occupied by macropores.

Preventing oxaliplatin-induced neuropathic pain: Using berberine to inhibit the activation of NF-κB and release of pro-inflammatory cytokines in dorsal root ganglions in rats.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious, undesirable effect of cancer treatment which is particularly difficult to prevent. Berberine and its derivatives have been reported to display robust antioxidant and analgesic effects in rat models of diabetic neuropathic pain and peripheral nerve injury. However, the analgesic role of berberine on oxaliplatin-induced CIPNP remains unknown. The present study aimed to explore the analgesic effect of berberine on CIPNP. Sprague Dawley rats were used to create the CIPNP animal model by oxaliplatin administration. Behavioral tests were performed by von Frey test, acetone drop test, hot plate test, and motor coordination. The protein expression levels of NF-κB p65 and phosphorylated p65 in dorsal root ganglions (DGRs) were detected by western blot analysis. Finally, TNF-α and IL-6 levels in DRGs were measured using specific ELISA kits. The results from the behavioral analysis demonstrated that a single injection of berberine ameliorated the mechanical and cold allodynia and thermal hyperalgesia in the model rats in a dose-dependent manner. Cumulative administration of berberine prevented the mechanical and cold allodynia and thermal hyperalgesia in the development of CIPNP induced by oxaliplatin. This prophylactic effect of berberine was associated with reduced phosphorylation of p65 and with decreased levels of pro-inflammatory cytokines IL-6 and TNF-α. The present study indicated that berberine may have a role in preventing the development of CIPNP and may serve as a therapeutic compound for the treatment of CIPNP.

Comparison and quantitative analysis of microstructure parameters between original loess and remoulded loess under different wetting-drying cycles.

The microstructural evolution of loess had a significant impact on the collapsibility of loess during wetting-drying cycles. Based on the analysis of scanning electron microscope (SEM) images by using Image-Pro Plus, the present study quantitatively compared the microstructural parameters of original loess and remoulded loess with different moisture content before and after wetting-drying cycles in size, shape, and arrangement. In size, the average diameter of both original loess particles and remoulded loess particles increased with the increasing of initial moisture content. However, the average diameter of original loess particles was slightly larger than that of remoulded loess particles before wetting-drying cycles. In contrast, the average diameter of both original loess particles and remoulded loess particles were very close to each other after three wetting-drying cycles. In shape, before wetting-drying cycles, the average shape factor of original loess particles was higher than that of remoulded loess particles. After three wetting-drying cycles, the difference in the average shape factor of both two loess samples with 5% initial moisture content is similar to that before wetting-drying cycles. Nevertheless, the average shape factor of both original loess particles and remouled loess particles with 15% initial moisture content were very close to that with 25% initial moisture content. In the arrangement, directional frequency indicated remoulded loess appeared to be more vertically aligned than original before and after three wetting-drying cycles. Furthermore, the directed anisotropy rate of remoulded loess was higher than that of the original loess before and after three wetting-drying cycles. In summary, the size, shape, and arrangement of both original loess particles and remoulded loess particles varied in different degrees before and after three wetting-drying cycles. Combined with the water retention curve of the loess, we analyzed the microstructural evolution mechanism of two loess particles during wetting-drying cycles. It is an excellent significance to study the engineering properties of original loess and remoulded loess.

[Effects of p-hydroxybenzoic acid and phloroglucinol on mitochondria function and root growth in cotton (Gossypium hirsutum L.) seedling roots.] / å¯¹ç¾ŸåŸºè‹¯ç”²é ¸å’Œé—´è‹¯ä¸‰é šå¯¹æ£‰èŠ±å¹¼è‹—æ ¹ç³»çº¿ç²’ä½“åŠŸèƒ½å’Œæ ¹ç³»ç”Ÿé•¿çš„å½±å“.

With early-maturing cotton cultivar CCRI-50 widely grown in China as experimental material, water culture experiment was conducted to study the effects of p-hydroxybenzoic acid and phloroglucinol with different concentrations (0.8, 4.0, and 20.0 mmol·L-1) on generation rate of reactive oxygen, changes of antioxidant enzyme activities and mitochondria function of cotton roots. Results showed that p-hydroxybenzoic acid and phloroglucinol treatments inhibited the cotton root growth, reduced SOD, POD, CAT and H+-ATPase activities in root mitochondria, increased the generation rate of O2-· and H2O2 content. In addition, they also increased the opening of mitochondrial permeability transition pores (MPTP), decreased the membrane fluidity and cytochrome c/a (Cyt c/a). Difference of mitochondria function between p-hydroxybenzoic acid and phloroglucinol treatments was minor at concentration of 0.8 mmol·L-1, while the inhibition to root growth and mitochondria function under treatment of p-hydroxybenzoic acid at concentration of 4.0 and 20.0 mmol·L-1 was stronger than that of phloroglucinol. Above all, p-hydroxybenzoic acid and phloroglucinol inhibited antioxidant enzyme activity and mitochondrial function in cotton seedling roots, and the inhibition depended on dose of phenolic acids. The inhibition to root growth and mitochondria function between p-hydroxybenzoic acid and phloroglucinol treatment was different, and p-hydroxybenzoic acid had stronger inhibition than phloroglucinol at the concentration more than 4.0 mmol·L-1.

Plant Volatiles Increase Sex Pheromone Attraction of Holotrichia parallela (Coleoptera: Scarabaeoidea).

Holotrichia parallela (Coleoptera: Scarabaeoidea) is a notorious pest of many crops. To improve the effectiveness of its female-produced sex pheromone (L-isoleucine methyl ester:(R)-(-)-linalool = 6:1), 14 plant volatiles, including dodecanoic acid, dodecanal, farnesol, α-farnesene, (Z)-3-hexen-1-ol, (E)-2-hexen-1-ol, (Z)-3-hexenyl acetate, (E)-2-hexenyl acetate, (R)-(+)-limonene, α-phellandrene, α-pinene, ocimene, methyl benzoate, and benzaldehyde, were individually evaluated using electroantennography and olfactometer assays. (E)-2-Hexenyl acetate and (Z)-3-hexenyl acetate were found to elicit the strongest responses in both males and females. Further testing of these two compounds in mixtures with the sex pheromone indicated that (E)-2-hexenyl acetate had a stronger synergistic effect than (Z)-3-hexenyl acetate. Field evaluations showed that mixtures of (E)-2-hexenyl acetate and the sex pheromone resulted in significantly higher catches than the sex pheromone alone. Using a 5:1 mixture of the sex pheromone and (E)-2-hexenyl acetate, the maximum number of females per trap per day was 14, showing a synergistic effect of a factor of four. For males, a 3:1 mixture of the sex pheromone and (E)-2-hexenyl acetate yielded a maximum number of 310 individuals per trap per day, equivalent to a synergistic effect of 175%. These results may provide the basis for the development of efficient pest management systems against H. parallela using plant volatiles and insect sex pheromones.

[Effects of brassinolide on leaf physiological characteristics and differential gene expression profiles of NaCl-stressed cotton].

This study analyzed the effects of brassinolide (BL) on Na⁺ accumulation, leaf physiological characteristics and differentially expressed genes (DEGs) of cotton leaves under NaCl stress. The results showed that NaCl stress increased the Na⁺, proline and MDA content in the leaves of Sumian 12 and Sumian 22, and changed the expression level of genes in cotton leaves. The application of BL counteracted the NaCl stress-induced growth inhibition in the two tested cotton cultivars. It reduced the accumulation of Na⁺, enhanced proline content, and resulted in a decrease in the MDA content of NaCl-stressed leaves, and the influence of BL on salt-stressed Sumian 12 plants was more pronounced than that on Sumian 22. The digital gene expression analysis in Sumian 12 indicated that BL application significantly influenced the gene expression in NaCl-stressed cotton leaves, the gene expression pattern as a result of the root applied BL on NaCl-stressed cotton treatment (BL+NaCl) was similar to the normal cotton plants (CK). Our results indicated that brassinolide alleviated NaCl stress on cotton through improving leaf physiological characteristics and gene expression, and resulted in an increase in biomass of NaCl-stressed cotton.

[Effects of nitrogen application rates on nitrogen uptake and utilization of direct-seeded cotton after wheat harvest].

An experiment was carried out to study the effects of different nitrogen application rates (0, 60, 120, 150, 180 and 240 kg N · hm⁻²) on the nitrogen uptake, utilization and distribution of short season cotton cultivar (CCRI-50) which was directly seeded after wheat harvest. Results showed that nitrogen application increased the nitrogen uptake of cotton at different growth stages, with the highest increment at the peak flowering-boll opening stage. Nitrogen application changed the percentages of nitrogen uptake among different growth stages. The percentages of nitrogen uptake decreased from seedling to peak flowering stage, but increased from peak flowering to boll maturing stage. In addition, nitrogen application reduced the decreasing speed of nitrogen concentration in middle and upper fruiting branches at later growth stages. Direct-seeded cotton had nitrogen and biomass accumulation in the lower and middle reproductive branches. With the nitrogen application of 150-180 kg · hm⁻², the lint yield, NARE (nitrogen apparent recovery efficiency) and the economic coefficient of biomass and nitrogen were relatively higher, and the eigenvalues of dynamic model of nitrogen content and nitrogen accumulation were relatively coordinate. Excessively high nitrogen application (over 180 kg N · hm⁻²) decreased biomass and nitrogen amount of reproductive organ in lower and middle branches, narrow rise of yield, and lower nitrogen use efficiency. However, excessively low nitrogen application (lower than 150 kg N · hm⁻²) also resulted in lower economic coefficient of biomass and nitrogen and yield. These results suggested the optimum nitrogen application rate 150-180 kg N · hm⁻² for direct-seeded cotton after wheat harvest in lower reaches of Yangtze River.

[Effects of nitrogen application rate on potassium uptake and utilization of direct-seeded cotton after wheat harvest]. / æ–½æ°®é‡å¯¹éº¦åŽç›´æ’­æ£‰é’¾ç´ å¸æ”¶åˆ©ç”¨çš„å½±å“.

By using cotton cultivar CCRI-50 as material, field experiments were conducted in the summer seasons of 2013 and 2014 at the experimental station of Jiangsu Academy of Agricultural Sciences (Nanjing, China) to study the effects of different nitrogen application rates (0, 60, 120, 150, 180 and 240 kg N·hm-2) on the potassium uptake and utilization of the cotton plant that was direct-seeded after wheat harvest. Data suggested that the elevated nitrogen application rates increased the cotton potassium uptake of all growth stages, and the largest increment was observed at the peak flowering-boll opening stage. Nitrogen application also changed the uptake percentage of potassium uptake of each stage, i.e., the percentage of potassium uptake decreased in the stage from seedling to peak flowering, while increased in the stage from peak flowering to boll maturing. In addition, the elevated nitrogen applications reduced the decreasing rate of nitrogen concentration in upper fruiting branches, but promoted the decreasing rate in middle and low fruiting branches at later growth stages. As the nitrogen application rate increased, the marginal effect of potassium uptake (promoted amount of potassium uptake due to 1 kg increase of N application) increased first and then decreased, and the lint production efficiency of potassium descended steadily. In cotton plants that were direct-seeded after wheat harvest, potassium and biomass were mainly accumulated in the lower and middle fruiting branches. At the 150 and 180 kg N·hm-2 application levels, much more potassium was allocated to the reproductive organs and the characters and the eigenvalues of simulated curves of potassium concentration and total potassium accumulation were more optimized than those at the higher or the lower N application levels. At the high nitrogen application (more than 180 kg N·hm-2) level, the marginal effect of potassium uptake and lint production efficiency decreased, and at the lower nitrogen application (less than 150 kg N·hm-2) level, lint yield was lower due to the decrease of economic coefficient of biomass and potassium in the middle and low fruiting branches.

[Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia].

OBJECTIVE: To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML). METHODS: The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test. RESULTS: The overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection. CONCLUSION: The HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.

Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukaemia. However, their efficacy has not been tested in a multicentre randomised controlled trial in a large population. We assessed the efficacy and safety of homoharringtonine-based induction treatment for management of newly diagnosed acute myeloid leukaemia. METHODS: This open-label, randomised, controlled, phase 3 study was done in 17 institutions in China between September, 2007, and July, 2011. Untreated patients aged 14-59 years with acute myeloid leukaemia were randomly assigned (by a computer-generated allocation schedule without stratification) to receive one of three induction regimens in a 1:1:1 ratio: homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and aclarubicin 20 mg/day on days 1-7 (HAA); homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and daunorubicin 40 mg/m(2) per day on days 1-3 (HAD); or daunorubicin 40-45 mg/m(2) per day on days 1-3 and cytarabine 100 mg/m(2) per day on days 1-7 (DA). Patients in complete remission were offered two cycles of intermediate-dose cytarabine (2 g/m(2) every 12 h on days 1-3). The primary endpoints were the proportion of patients who achieved complete remission after two cycles of induction treatment and event-free survival in the intention-to-treat population. The trial is registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. FINDINGS: We enrolled 620 patients, of whom 609 were included in the intention-to-treat analysis. 150 of 206 patients (73%) in the HAA group achieved complete remission versus 125 of 205 (61%) in the DA group (p=0.0108); 3-year event-free survival was 35.4% (95% CI 28.6-42.2) versus 23.1% (95% CI 17.4-29.3; p=0.0023). 133 of 198 patients (67%) in the HAD group had complete remission (vs DA, p=0·20) and 3-year event-free survival was 32.7% (95% CI 26.1-39.5; vs DA, p=0.08). Adverse events were much the same in all groups, except that more patients in the HAA (12 of 206 [5.8%]) and HAD (13 of 198 [6.6%]) groups died within 30 days than in the DA group (two of 205 [1%]; p=0.0067 vs HAA; p=0.0030 vs HAD). INTERPRETATION: A regimen of homoharringtonine, cytarabine, and aclarubicin is a treatment option for young, newly diagnosed patients with acute myeloid leukaemia. FUNDING: Chinese National High Tech Programme, Key Special Research Foundation of the Ministry of Science and Technology of China, National Nature Science Foundation of China, National Clinical Key Specialty Construction Project.

[Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1].

OBJECTIVE: To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines. METHODS: The phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS). The effect of HHT on leukemia stem-like cells with immunophenotype of CD34(+)CD38(-)CD96(+) was detected with FACS. Cell growth was measured by MTT assay. Activation of Caspase pathway and expression of apoptosis-related regulator proteins were examined by Western blotting. RESULTS: FACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34(+)CD38(-)CD96(+), while 26.7% on Kasumi-1 cells expressed this marker. In contrast,U937 cells showed CD96 negative. HHT significantly inhibited cell growth of KG-1 cells with an IC(50) of 16.9 ng/ml at 48 h. The ratio of CD34(+)CD38(-)CD96(+) cells decreased from 63.6% to 17.1% after HHT treatment. Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphorylated-Akt. CONCLUSION: HHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphorylated-Akt.