Smart Targeted Delivery Systems for Enhancing Antitumor Therapy of Active Ingredients in Traditional Chinese Medicine.

As a therapeutic tool inherited for thousands of years, traditional Chinese medicine (TCM) exhibits superiority in tumor therapy. The antitumor active components of TCM not only have multi-target treatment modes but can also synergistically interfere with tumor growth compared to traditional chemotherapeutics. However, most antitumor active components of TCM have the characteristics of poor solubility, high toxicity, and side effects, which are often limited in clinical application. In recent years, delivering the antitumor active components of TCM by nanosystems has been a promising field. The advantages of nano-delivery systems include improved water solubility, targeting efficiency, enhanced stability in vivo, and controlled release drugs, which can achieve higher drug-delivery efficiency and bioavailability. According to the method of drug loading on nanocarriers, nano-delivery systems can be categorized into two types, including physically encapsulated nanoplatforms and chemically coupled drug-delivery platforms. In this review, two nano-delivery approaches are considered, namely physical encapsulation and chemical coupling, both commonly used to deliver antitumor active components of TCM, and we summarized the advantages and limitations of different types of nano-delivery systems. Meanwhile, the clinical applications and potential toxicity of nano-delivery systems and the future development and challenges of these nano-delivery systems are also discussed, aiming to lay the foundation for the development and practical application of nano-delivery systems of TCM in clinical settings.

Whole genome analysis of Enterobacter cloacae Rs-2 and screening of genes related to plant-growth promotion.

The genus Enterobacter is widely recognized for its biotechnology potential in improving soil environment and crop growth promotion. To further explore these biotechnological potentials, we sequenced and analyzed the whole genome of Enterobacter cloacae Rs-2. The analysis showed that the total length of the Rs-2 genome was 6,965,070,514 bp, and GC content was 55.80%; the annotation results of GO and COG databases showed that the genome contains a variety of growth-promoting genes, such as iscU, glnA, glnB (nitrogen fixation); iucABCD (siderophore synthesis) and fepA, fcuA, fhuA, and pfeA, etc. (siderophore transport); ipdC (secreted IAA) and gcd, pqqBCDEF (dissolved phosphorus), etc. No pathogenic factors such as virulence genes were found. The application of Rs-2 as a soil inoculant in pot experiments showed great potential for growth promotion. This study proved the plant growth-promoting ability of Rs-2 at the molecular level through genetic screening and analysis, which provided guidance for the further improvement of the strain and laid a foundation for its application in agricultural production.

Systematic Identification and Analysis of OSC Gene Family of Rosa rugosa Thunb.

The oxidosqualene cyclase family of Rosa rugosa (RrOSC) provides a starting point for the triterpenoid pathway, which contributes to the medicinal value of the extraction of tissues of Rosa rugosa. However, the structure and function of key RrOSCs of active triterpenoids remain ambiguous. In this study, a total of 18 RrOSC members with conservative gene structures and motifs were identified based on the genome of Rosa rugosa. The RrOSCs were located on three chromosomes including two gene clusters that derived from gene replication. The phylogenetic relationship divided RrOSCs into six groups, and the RrOSCs of GI and GIV that were represented by lupeol or α-amyrin were identified as likely to include candidate genes for producing active triterpenoids. Considering the high expression or specific-tissue expression of the candidates, RrOSC1, RrOSC10, RrOSC12, and RrOSC18 were considered the key genes. RrOSC12 was identified in vitro as lupeol synthase. The results provided fundamental information and candidate genes for further illustration of the triterpenoid pathway involved in the pharmacological activities of Rosa rugosa.

The 45-month therapy outcomes of permanent seed implantation and radical prostatectomy for prostate cancer patients.

Objective To compare the efficacy and safety-related outcomes after radical prostatectomy (RP) and permanent seed implantation (PI) using iodine-125 seeds in patients with prostate cancer. Method A retrospective analysis of 196 patients with biopsy-confirmed prostate cancer (T2-T3) was performed in this study. Forty-five patients who underwent PI using iodine-125 seeds combined with endocrine therapy or androgen deprivation therapy (ADT) were compared with 151 patients who underwent RP combined with endocrine therapy or adjuvant ADT. The efficacy and safety outcomes were compared using Kaplan-Meier curves and t-tests. Results Between the RP and PI treatment modalities, no significant difference (P > 0.05) in biochemical recurrence-free survival (BRFS) was observed using Kaplan-Meier curves, regardless of the combination of adjuvant treatment modalities. Furthermore, no significant differences were observed (P > 0.05) with respect to PSA fluctuations, albumin, leukocyte count, urinary and rectal symptoms, erectile function or quality of life (QoL) between the two therapy methods. However, significant differences in the maximum flow rate, average length of hospital stay and indwelling catheter time were observed between the two groups (P < 0.001). Conclusion Iodine-125 seed implantation significantly shortened the average length of hospital stay and indwelling catheter time compared with RP, and the haemoglobin level was significantly higher in the PI group than in the RP group; however, the maximum urine flow rate was lower after of PI than after RP. These two methods showed similar BRFS rates among prostate cancer patients.

Arbutin Ameliorates Murine Colitis by Inhibiting JAK2 Signaling Pathway.

Background and objective: Abnormal activation of Janus kinase 2 (JAK2) promotes the pathogenesis and progress of inflammatory bowel disease (IBD) by stimulating the cytokine traffic. Based on docking studies, arbutin, a natural product extracted from a traditional medicinal plant bearberry, was found to bind to JAK2. The study aimed to investigate the effects and mechanisms of regulating JAK2 by arbutin on colitis in mice. Methods: A mice colitis model was established to mimic human IBD. The mice freely drank water containing dextran sulfate sodium. Inflammation in epithelial (IEC6) and immune (RAW264.7) cells was analyzed following treatment with lipopolysaccharides (LPS). Results: Colitis symptoms, including body weight loss, increased disease activity index, and increased colon weight/length ratio, were significantly alleviated by arbutin. Mediators of colonic pro-inflammatory cytokines as well as apoptosis markers in colitis were suppressed by the glycoside. High expression of phosphorylated JAK2 in colitis was significantly reversed by arbutin. The effects of arbutin treatment on colitis were considerably inhibited by the JAK2 inhibitor AG490. LPS-induced inflammatory responses were also suppressed by arbutin, which was notably inhibited by the JAK2 inhibitor AG490. Conclusion: The findings obtained herein suggest the protective role of arbutin and provide novel insights into alternative colitis treatments, which involve inhibition of the JAK2 signaling pathway.

[Plasmakinetic enucleation of the prostate versus holmium laser enucleation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To evaluate the clinical effects of plasmakinetic enucleation of the prostate (PKERP) and holmium laser enucleation of the prostate (HoLEP) in the treatment of BPH. METHODS: We retrospectively analyzed the clinical data on 78 BPH patients treated by PKERP (n = 38) or HoLEP (n = 40) from January 2016 to October 2017. We recorded the operation time, intraoperative hemoglobin level, catheter-indwelling time, bladder irrigation time, hospital stay, 6-month postoperative IPSS, quality of life (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR), PSA level, International Index of Erectile Function (IIEF) and postoperative complications, and compared the obtained parameters between the two groups and some of them with the baseline. RESULTS: In comparison with the baseline, both the PKERP and HoLEP groups showed statistically significant differences at 6 months after surgery in the QOL score (4.82 ± 0.56 and 4.70 ± 0.67 vs 2.44 ± 0.69 and 2.92 ± 0.49, P < 0.01), IPSS (19.52 ± 4.96 and 19.44 ± 4.08 vs 9.56 ± 2.5 and 9.81 ± 2.5, P < 0.01), Qmax (ï¼»4.54 ± 1.86ï¼½ and ï¼»4.42 ± 2.89ï¼½ ml/s vs ï¼»17.72 ± 3.46ï¼½ and ï¼»17.27 ± 4.42ï¼½ ml/s, P < 0.01), and PVR (ï¼»83.73±55.33ï¼½ and ï¼»109.65 ± 89.58ï¼½ ml vs ï¼»19.93 ± 11.07ï¼½ and ï¼»18.31 ± 15.03ï¼½ ml, P < 0.01). Statistically significant differences were also found between the PKERP and HoLEP groups in the reduced hemoglobin level (ï¼»21.04 ± 16.96ï¼½ vs ï¼»7.88 ± 6.65ï¼½ g/dl, P = 0.01), catheter-indwelling time (ï¼»7.67 ± 2.27ï¼½ vs ï¼»3.93 ± 2.18ï¼½ d, P = 0.01), bladder irrigation time (ï¼»1.67 ± 0.62ï¼½ vs ï¼»1.3 ± 0.54ï¼½ d, P = 0.05), hospital stay (ï¼»4.22 ± 1.55ï¼½ vs ï¼»3.26 ± 0.9ï¼½ d, P = 0.01), and 6-month postoperative QOL score (ï¼»2.44 ± 0.69ï¼½ vs ï¼»2.92 ± 0.49ï¼½, P = 0.05), but not in the other parameters. CONCLUSIONS: Both PKERP and HoLEP are safe and effective for the treatment of BPH, the former more feasible in primary hospitals, while the latter with the advantages of less bleeding, shorter catheterization and hospital stay, and higher 6-month postoperative QOL score.

Negative-Pressure Cavitation Extraction of Secoisolariciresinol Diglycoside from Flaxseed Cakes.

The negative-pressure cavitation extraction (NPCE) technique was applied firstly to extract secoisolariciresinol diglucoside (SDG) from flaxseed cakes. The significant extraction parameters were screened by fractional factorial design (FFD). The optimal parameters were determined using the central composite design (CCD) with the two variables, NaOH amount and the liquid/solid ratio. The conditions of the extraction were optimized by using response surface methodology (RSM). Under the optimal conditions, the extraction yield and the extraction purity of SDG was 16.25 mg/g and 3.86%, respectively. The efficiency of NPCE was compared with that of conventional extraction methods. Our results demonstrated that NPCE was comparable to the well-known ultrasound-assisted extraction in term of extraction yield and purity. This extraction technique has advantages of less time-consuming, low solvent usage and high throughput capability.

Novel therapeutic approach for neurogenic erectile dysfunction: effect of neurotrophic tyrosine kinase receptor type 1 monoclonal antibody.

BACKGROUND: Erectile dysfunction (ED) is a major health issue in aged populations, and neurogenic ED is particularly difficult to treat. Novel therapeutic approaches are needed for treatment of neurogenic ED of peripheral origin. OBJECTIVE: To investigate the therapeutic effects of a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile function and sexual behavior in a rat model of cavernous nerve injury (CNI). DESIGN, SETTING, AND PARTICIPANTS: In one experiment, 84 male rats were randomly assigned to seven groups. The groups underwent either CNI or sham surgery, subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations immediately after surgery and then 1 wk later. Erectile function was assessed and histologic/molecular analyses were performed at 6 wk after surgery. In a second experiment, 36 male rats were randomly divided into three groups. The groups underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the performance of the rats in sexual behavior tests was videotaped. INTERVENTION: CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA-mAb. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The intracavernous pressure response to cavernous nerve electrostimulation was measured and midpenile cross-sections were histologically examined. Western blotting (WB) of cavernous tissue protein was performed. Rats were assessed for chasing, mounting, intromission, and ejaculation behaviors during sexual behavior tests. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramer t test. RESULTS AND LIMITATIONS: Recovery of erectile function of varying degrees was observed in the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine hydroxylase-positive nerve fibers in the corpus cavernosum and enhanced neuronal nitric oxide synthase-positive fibers in the dorsal nerve. The ratio of smooth muscle to collagen in the corpus cavernosum was significantly improved in TrkA-mAb treatment groups compared to PBS vehicle and IgG control groups. WB confirmed these biological changes. There was a nonsignificant increase in the average number of intromissions and ejaculations in the TrkA-mAb group. The study limitations include small sample size, variability in sexual behavior, lack of data on the neuromuscular mechanism involved, and lack of information of the role of neurotrophins or cytokines in regeneration. CONCLUSIONS: TrkA-mAb successfully inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on ED and sexual behavior disorder in a rat model of CNI. PATIENT SUMMARY: This report provides strong evidence that a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on erectile dysfunction and sexual behavior disorder in a rat model of cavernous nerve injury. The results raise the possibility that human patients with neurogenic erectile dysfunction may respond to TrkA-mAb in a manner that parallels the response seen in our rodent study.

Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).

The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•- quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63-5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

[Observation on therapeutic effect of peripheral facial paralysis treated by string puncture combined with electroacupuncture].

OBJECTIVE: To explore the effective treatment of peripheral facial paralysis. METHODS: Ninety-five cases of peripheral facial paralysis were randomly divided into an observation group (48 cases) and a control group (47 cases). In observation group, the acupoints located on paralyzed muscle, such as Yangbai (GB 14), Taiyang (EX-HN 5), Tongziliao (GB 1), Jiache (ST 6) and Dicang (ST 4), etc. were selected; string puncture was applied and the body of needles went through the muscular layer at 40 degrees-60 degrees angle with the direction of muscle fiber; Yangbai (GB 14), Taiyang (EX-HN 5) etc. were selected for electroacupuncture. In control group, the same acupoints and routine manipulations were applied. The clinical therapeutic effects, courses and the House-Brackmann (H-B) facial nerve function grading of both groups were compared. RESULTS: The total effective rate in observation group was 100.0% (47/47) which was superior to 93.6% (44/47) in control group (P < 0.01); the average effective, marked effective and cured durations of cured patients in observation group were much shorter than those in control group (all P < 0.01); the H-B facial nerve function grading of both groups were improved after treatment (all P < 0.01), and more significant in observation group (P < 0.01). CONCLUSION: By string puncture therapy, peripheral facial paralysis is treated more effective than that by routine puncture, and the curative courses are obviously shortened.

[Effect of Danshensu on fibronectin and collagen-1 secretion induced by high glucose in human peritoneal mesothelial cells].

OBJECTIVE: To investigate the possible role of Danshensu on fibronectin (FN) and collagen-I (Col-I) secretion induced by high glucose in human peritoneal mesothelial cells (HPMCs). METHODS: HPMCs were treated with high glucose and Danshensu at different concentrations. The mRNA expression of FN, Col-I, endothelin-1 (ET-1), and heme oxygenase-1 (HO-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of FN, Col-I HO-1 and ET-1 were analyzed by enzyme-linked immunosorbent assay or immunofluorescence method. RESULTS: The expression of protein and mRNA of FN and Col-I were attenuated by Danshensu in both dose-dependent and time-dependent manner. The mRNA and protein levels of ET-1 were decreased, and the mRNA and protein levels of HO-1 increased in the Danshensu groups in a dose-dependent manner compared with the high glucose group. The expression of ET-1 and HO-1 showed little difference in a time gradient of danshensu(P>0.05). CONCLUSION: Danshensu can protect HPMCs through inhibiting the expression of FN and Col-I induced by high glucose, which is related to the suppression of oxidative stress.

Effect of Al2O3 mole fraction and cooling method on vitrification of an artificial hazardous material. Part 1: variation of crystalline phases and slag structures.

This study investigated how Al ions affect slag structure. During vitrification, pure Al(2)O(3), CaO, and SiO(2) served as the encapsulation phases with the use of Al mol% as an operating parameter. All specimens with the same basicity (mass ratio of CaO to SiO(2)) of 2/3 were vitrified at 1400 degrees C and cooled by air cooling or water quenching. XRD was used to measure the volume fractions of crystalline and amorphous phases. In a non-Al environment, CaSiO(3) was formed in air-cooled and water-quenched slags. With the addition of Al(2)O(3), no crystalline phases were observed in water-quenched slags. With the increase of Al mol% in specimens, the Al ions in air-cooled slags initially acted as an intermediate linking one tetrahedron chain to another and reducing the amount of crystalline phase, then behaved as a network former making the slags amorphous, and finally replaced Si ions in silicate frames to generate a large amount of CaAl(2)Si(2)O(8). Air cooling improved the formation of crystallize structures with more leachable metal ions. A highly crystallized Al-framed structure is not suitable for encapsulating hazardous metals in vitrified slags.

Effect of Al2O3 mole fraction and cooling method on vitrification of an artificial hazardous material. Part 2: encapsulation of metals and resistance to acid.

This study investigated the encapsulation of metals in vitrified slags using a sequential extraction procedure and how Al ions and slag structure affected the encapsulation of heavy metals. It is found that the substitution of Al ions for Si ions weakened the encapsulation of the glass matrix due to the relatively weaker single bond strength of Al-O. In addition, the substitution also governed the phase distribution of metals that tended to stay slags. In comparison to air cooled slags, water quenched slags were more amorphous and offered relatively better encapsulation of metals. These findings were also supported by the SEM observation and XRD analysis. Although Al(2)O(3) may connect the non-bridging oxygen and polymerize the slag structure, the excess addition of Al(2)O(3) reduced the metal encapsulation and acid resistance of slags.

[Relevant low toxicities with rhG-CSF mobilized and cryopreserved autologous peripheral blood stem cell return infusions in children].

The purpose of this study was to evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) fractionated return infusions in children. 35 children patients with malignant tumors (13 acute leukaemias, 15 neuroblastomas and 7 malignant lymphomas) received fractionated return infusions of cryopreserved stem cells after undergoing high-dose chemotherapy without or with total body irradiation. The toxicities of 70 return infusions were evaluated. All patients were mobilized by chemotherapy plus recombination human granulocyte colony-stimulating factor (rhG-CSF), and then PBSCs were collected by a separator CS-3000 plus or COBE spectra-4. The grafts were cryopreserved in 10% dimethyl sulfoxide (DMSD) and stored in liquid nitrogen. There were totally 70 PBSC transfusions. The total volume of PBSCs transfused: 190 - 420 ml (265 +/- 73 ml or 13.7 +/- 4.2 ml/kg) with a mean of (4.43 +/- 1.91) x 10(8)/kg of PBSCs, and 0.94 +/- 0.18 g/kg of DMSO. The single dose: 90 - 300 ml (132 +/- 37 ml or 6.6 +/- 5.2 ml/kg) with a mean of 0.68 +/- 0.12 g/kg of DMSO. Symptoms occurring during the infusions were recorded. All patients were monitored for 24 hours after infusion. Pulse, blood pressure, body temperature, and respiratory rate were recorded every 15 minutes. At four hours before and 8 hours after infusion, urinalysis was performed. Serum potassium, sodium, creatinine, total bilirubin, aspartate amino transferase (AST), and alanine amino transferase (ALT) levels were examined within 24 hours before and after the first infusion. The results showed that the toxicities observed included hemoglobinuria in 54 return infusions (77.1%), headache in 28 (40.0%), nausea in 24 (34.3%), vomiting in 17 (24.3%), and abdominal pain in 8 (11.4%). Patients who received a graft > 200 ml tended to have a higher frequency of hemoglobinuria, headache, nausea, vomiting, or abdominal pain (P<0.01), and they disappeared quickly, too. Total bilirubin increased after the first return infusion (P<0.01), and there was a significant correlation between the volume of infusion and the degree of total bilirubin increase (r=0.8977, P<0.01). No renal failure or shock occurred. It is concluded that transient hemoglobinuria, headache, nausea, vomiting, and abdominal pain are common toxicities associated with PBSC autograft, and these toxicities are related with a single volume of PBSCs transfused. Total bilirubin increase is correlated with the volume of infusion. In a word, the toxicity is less frequent and lower severe in children with fractionated infusions of cryopreserved peripheral blood stem cell.

[Long-term effect of high dose chemotherapy combined with stem cell transplantation on stage IV neuroblastoma in children].

OBJECTIVE: Neuroblastoma is a highly malignant tumor. Stage IV neuroblastoma has a very poor long-term outcome by conventional chemotherapy and surgery and better therapies are essential. This study aimed to explore the long-term effect of high dose induction chemotherapy combined with autologous peripheral blood stem cell transplantation and 13-cis retinoid acid treatment on stage IV neuroblastoma in children. METHODS: Twenty-eight children with stage IV neuroblastoma, aged 2.1-11.5 years (mean 3.3 +/- 1.9 years), were employed for the study. Primary sites of the tumors included adrenal (n=23), chest (n=3), chest-abdomen (n=1) and sacrum (n=1). Before autologous peripheral blood stem cell transplantation the patients received 6 courses of intensive induction chemotherapy. During chemotherapy the autologous peripheral blood stem cells were harvested and the tumor excision was done. After transplantation the local radiation and 13-cis retinoid acid therapy were administered. RESULTS: After 6 courses of induction chemotherapy 13 patients got complete remission (CR), 11 got partial remission (PR), and 4 had no response. The 24 patients who received CR or PR completed the full therapy. A 3.5 +/- 0.7 years follow-up showed that the 4-year event-free survival of the CR and PR patients was 29.2%. The median no-relapse survival time in CR patients was 4.1 +/- 0.7 years but 2.8 +/- 0.5 years in PR patients (t= 3.9, P < 0.01). CONCLUSIONS: High dose chemotherapy combined with autologous peripheral stem cell transplantation and 13 cis-retinoid acid treatment can improve the long-term outcome of patients with stage IV neuroblastoma. The patients in CR before transplantation had better outcomes than those in PR.

Apex-to-base dispersion in regional timing of left ventricular shortening and lengthening.

OBJECTIVES: We investigated whether the onset and progression of regional left ventricular (LV) shortening and lengthening parallel the apex-to-base differences in depolarization and repolarization. BACKGROUND: Limited information exists regarding apex-to-base differences in longitudinal and circumferential deformation sequence of the LV. METHODS: The apex-to-base differences in electric activation and the progression of longitudinal and circumferential shortening and lengthening sequences were determined in 8 porcine beating hearts in situ by implanting bipolar electrodes and an array of 14 sonomicrometry crystals in the LV free wall. RESULTS: Electric activation started at the apical subendocardium and showed significant delay in reaching the LV base. The onsets of mechanical activation and subsequent 20%, 40%, and 80% peak longitudinal shortenings required longer time to occur at base compared to the apex. The repolarization sequence propagated in reverse, with the base repolarizing before the apex. Subendocardial longitudinal shortening at base and subepicardial circumferential shortening at apex continued beyond the period of LV ejection, resulting in an apex-to-base gradient in the onset of lengthening. This gradient correlated with the duration of isovolumic relaxation (r = 0.85, p = 0.004) and the time required for reaching the lowest LV diastolic pressure (r = 0.70, p = 0.04). CONCLUSIONS: Apex-to-base delay in mechanical shortening of LV parallels the apex-to-base direction of the electric activation sequence. Basal subendocardial and apical subepicardial regions deform through a characteristic phase of postsystolic shortening. Short-lived apex-to-base and subendocardial-to-subepicardial relaxation gradients at the onset of diastole may have a physiologic significance in facilitating active restoration of the LV cavity in diastole.

[Treatment of high-risk neuroblastoma with intensive chemotherapy, autologous peripheral blood stem cell transplantation, and 13-cis-retinoic acid].

OBJECTIVE: The prognosis for neuroblastoma in advanced stage is still poor, even under conventional chemotherapy. This study aimed to investigate if very high dose chemotherapy in conjunction with autologous peripheral blood stem cell transplantation and 13-cis-retinoic acid could get excellent results in children with high risk neuroblastoma. METHODS: Six children, aged from 4 to 8 years, with stage IV neuroblastoma were included in the study. The duration of the illness before admission was 1 to 12 months. Primary sites of the diseases were in the abdominal cavity (n = 5) and thoracic cavity (n = 1). All of patients had bone marrow metastasis, and one had multiple bone metastasis and orbital metastasis. All of the patients received very high dose chemotherapy, surgery, local radiation (20-30 Gy), and autologous peripheral blood stem cell transplantation as well as 13-cis retinoic acid. Induction chemotherapy included vincristine 0.67 mg/(m2 x 24 h, x 3), cyclophosphamide 2.1 g/(m2 x 24 h, x 2) and doxorubicin 25 mg/(m2 x 24 h, x 3) for 4 courses. Drugs were given as 24 hour-continuous intravenous infusion. Etopside 200 mg/(m2 x 24 h, x 3) and cisplatin 50 mg/(m2 x 24 h, x 3) were given for 2 courses. Conditioning regimen included carboplatin 400 mg/(m2.d) for 4 days, etoposide 300 mg/(m2.d) for 4 days and melphalan 70 mg/(m2.d) for 3 days. 13-cis retinoic acid 160 mg/(m2.d) started on +59 days for 6 courses, each course including 14 days therapy and 14 days rest. RESULTS: Six patients got a complete response before stem cell transplantation. Their bone marrow metastasis disappeared and so did bone and orbital metastasis. However, marrow suppression due to very high dose chemotherapy occurred in all of the patients, which lasted for 3-4 weeks for peripheral leukocyte recovery. Fever occurred after they finished 1/3 course of chemotherapy. Infection, however, was cured with the use of Fortum and Imipenem, ect. Autologous peripheral blood stem cell transplantation was initiated and successful in all cases. Follow-up studies revealed that all the patients were in CR status 4-18 months after transplant, and the cardiac and liver and renal functions were normal. Meanwhile, bone marrow was recovered or in the process of recovery. CONCLUSION: The new strategies focused on very high dose chemotherapy, autologous peripheral blood stem cell transplantation and biological therapy might be a good option for patients with advance neuroblastoma.