The Curie temperature: a key playmaker in self-regulated temperature hyperthermia.

The Curie temperature is an important thermo-characteristic of magnetic materials, which causes a phase transition from ferromagnetic to paramagnetic by changing the spontaneous re-arrangement of their spins (intrinsic magnetic mechanism) due to an increase in temperature. The self-control-temperature (SCT) leads to the conversion of ferro/ferrimagnetic materials to paramagnetic materials, which can extend the temperature-based applications of these materials from industrial nanotechnology to the biomedical field. In this case, magnetic induction hyperthermia (MIH) with self-control-temperature has been proposed as a physical thermo-therapeutic method for killing cancer tumors in a biologically safe environment. Specifically, the thermal source of MIH is magnetic nanoparticles (MNPs), and thus their biocompatibility and Curie temperature are two important properties, where the former is required for their clinical application, while the latter acts as a switch to automatically control the temperature of MIH. In this review, we focus on the Curie temperature of magnetic materials and provide a complete overview beginning with basic magnetism and its inevitable relation with Curie's law, theoretical prediction and experimental measurement of the Curie temperature. Furthermore, we discuss the significance, evolution from different types of alloys to ferrites and impact of the shape, size, and concentration of particles on the Curie temperature considering the proposed SCT-based MIH together with their biocompatibility. Also, we highlight the thermal efficiency of MNPs in destroying tumor cells and the significance of a low Curie temperature. Finally, the challenges, concluding remarks, and future perspectives in promoting self-control-temperature based MIH to clinical application are discussed.

CT/MR detectable magnetic microspheres for self-regulating temperature hyperthermia and transcatheter arterial chemoembolization.

The embolic microspheres containing magnetic nanoparticles and anti-tumor drugs have been proposed for transcatheter arterial chemoembolization (TACE). However, this technique still suffers the poor control of hyperthermia temperature and drug release behavior. Herein, the magnetic microspheres based on low Curie temperature superparamagnetic iron oxide nanoparticles are developed by emulsification cross-linking of gelatin, genipin, and sodium alginate. The magnetic microspheres can self-regulate the hyperthermia temperature at around 50°C, un-necessitating any temperature control facilities. The magnetic microspheres can load doxorubicin hydrochloride and the loaded drug can be released in a controllable way by using an alternating magnetic field. Cytocompatibility and hemolysis evaluations confirm the non-cytotoxicity and negligible hemolysis of magnetic microspheres. The embolization model on rabbit auricular artery demonstrates that the magnetic microspheres can occlude the targeted blood vessel and are visualized under CT/MR imaging. All these findings suggest that the prepared magnetic microspheres could be used as the embolic agent in TACE. STATEMENT OF SIGNIFICANCE: The existing magnetic embolic microspheres suffer the poor control of hyperthermia temperature and drug release behavior in TACE. In this work, we developed the magnetic embolic microspheres based on superparamagnetic iron oxide nanoparticles with a low Curie temperature. Upon the application of alternating magnetic field, the embolic microspheres can self-regulate the hyperthermia temperature at around 50°C and the drug loaded in the microspheres can be released in a somewhat controllable manner. The embolic microspheres are also detectable to both CT and MR. These characteristics enable the developed microspheres to simultaneously realize self-regulating temperature hyperthermia, on-demand drug release, embolization, and CT/MR imaging.

The heating efficiency of magnetic nanoparticles under an alternating magnetic field.

Hysteresis loss and relaxation loss are the two dominant heating mechanisms of magnetic nanoparticles (MNPs) in an alternating magnetic field (AMF). In magnetic induction hyperthermia, heating efficiency is one of the crucial factors. It is proposed that the MNPs with a dominant heating mechanism of relaxation loss will exhibit a higher heating efficiency. However, the relative experiments supporting the proposal is still absent due to the difficulty of obtaining the MNPs with the same components and similar morphology but different dominant heating mechanism. Here, the post-processing method of calcination is employed to change the cation distribution of the MNPs (Fe3O4 and Zn0.54Co0.46Cr0.6Fe1.4O4), so as to obtain the MNPs with similar morphology but different dominant heating mechanism. The magnetic heating experiments were conducted to examine the heating efficiency. The results suggest that the MNPs with relaxation loss have a higher heating efficiency under the investigated AMF.

Magnetic hydrogel with long in situ retention time for self-regulating temperature hyperthermia.

Aim: Magnetic hydrogels (MHGs) have been proposed to avoid the redistribution and loss of magnetic nanoparticles (MNPs) when administrated by intratumoral injection. However, the requirement of complex cooling systems and temperature monitoring systems still hinder the clinical application of MHGs. This study investigates the feasibility of developing an MHG to realize the self-regulation of hyperthermia temperature. Methods: The MHG was developed by dispersing the MNPs with self-regulating temperature property into the temperature-sensitive hydrogel through physical crosslinking. The MHG's gelation temperature was tested by measuring the storage modulus and loss modulus on a rotational rheometer. The biocompatibility of the MHG and MNPs was characterized by CCK-8 assay against HaCaT cells. The in vivo magnetic heating property was examined through monitoring the temperature in the MHG on mice back upon the application of the alternating magnetic field (400 ± 5 Oe, 100 ± 5 kHz) every week for successive six weeks. Results: The gelation temperature of the MHG falls in 28.4°C-37.4°C. At in vivo applied concentration of 80 mg/mL, the MHG exhibits over 80% cell viability after 72 h, significantly higher than 50% cell viability of the MNPs (p<0.001). The MHG's stable magnetic hyperthermia temperatures in vivo are in the range of 43.4°C-43.8°C. Conclusions: The developed MHG can be injected using a syringe and will solidify upon body temperature. The biocompatibility is improved after the MNPs being made into MHG. The MHG can self-regulate the temperature for six weeks, exhibiting application potential for self-regulating temperature hyperthermia.

Efficacy of Intensive Acupuncture Versus Sham Acupuncture in Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). METHODS: In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement. RESULTS: Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. CONCLUSION: Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up.

The efficacy of Tung's acupuncture for sex hormones in polycystic ovary syndrome: A randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine disorder in reproductive-age women. Tung's acupuncture, a Traditional Chinese Medicine (TCM) treatment, is widely used for PCOS in East Asia, but evidence on its efficacy is rare. The aim of this RCT study was to examine whether the Tung's acupuncture could be a complementary treatment method for PCOS. METHODS: A total of 60 PCOS patients were randomly assigned to a Tung's acupuncture group (n = 30) or a cyproterone acetate/ethinylestradiol (CPA/EE) group (n = 30). Each participant received treatments for 12 weeks to assess the short-term treatment efficacy and then followed up for another 12 weeks to assess the long-term treatment efficacy. The primary outcome examined was change in the ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH); the secondary outcomes examined were changes in body mass index (BMI), LH, FSH, total testosterone (TT), ovarian volume, polycystic ovary number and menstrual frequency. RESULTS: Both groups showed significant reductions in the LH/FSH ratio, LH and TT after 12-week treatment (p < 0.001) and 12-week follow-up (p < 0.05). No significant differences existed between the two groups (p > 0.05). Both groups showed significant improvement in BMI, menstrual frequency and polycystic ovary number after 12-week treatment (p < 0.05). CONCLUSION: Compared with CPA/EE, Tung's acupuncture showed no better improvement on LH/FSH ratio for PCOS although it could reduce the ratio. Tung's acupuncture might have some effect on long-term weight control and menstruation frequency. Further studies addressing this study's limitations are recommended.

Correction to: Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: study protocol for a randomised controlled trial.

After publication of the original article [1], the authors have notified us that the Trial registration number NCT03274713 should be replaced by NCT03366363 in the Abstract section of the paper.

Efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for knee osteoarthritis: study protocol for a randomised controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Although the available evidence for its efficacy is inconclusive, acupuncture is used as an alternative therapy for KOA. The aim of this trial is to determine the efficacy of electro-acupuncture and manual acupuncture versus sham acupuncture for KOA. METHODS/DESIGN: This is a study protocol for a randomised, three-arm, multicentre, clinical trial. A total of 480 patients with KOA will be randomly assigned to the electro-acupuncture group, the manual acupuncture group or the sham acupuncture group in a 1:1:1 ratio. All patients will receive 24 sessions over 8 weeks. Participants will complete the trial by visiting the research centre at week 26 for a follow-up assessment. The primary outcome is the success rate: the proportion of patients achieving a minimal clinically important improvement, which is defined as ≥2 points on the numerical rating scale and ≥6 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Secondary outcomes include the numerical rating scale, WOMAC score, global patient assessment and quality of life at weeks 4, 8, 16 and 26 after randomisation. DISCUSSION: This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of KOA. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03274713 . Registered on 20 November 2017.

Effects of maternal mild zinc deficiency and different ways of zinc supplementation for offspring on learning and memory.

BACKGROUND: The effect of different ways of zinc supplementation on spatial learning and memory remains unclear. OBJECTIVES: This study aims to assess the effectiveness of two ways of zinc supplementation - oral use and intravenous transfusion - in zinc-deficient offspring rats on learning and memory. DESIGN: Rats were randomly divided into six groups on the first day of pregnancy (n=12): control (CO), pair fed (PF), zinc deprived (ZD), oral zinc supplementation (OZS), injection zinc supplementation (IZS), and injection control. The offspring's spatial learning and memory were tested at postnatal day 35 using Morris water maze (MWM). Maternal rats' serum zinc was measured at postnatal day 21, while pups' serum zinc was measured at postnatal day 35. RESULTS: Compared with the CO and PF groups, pups in ZD group spent more time finding the latent platform and swam longer distances (p<0.05). Compared with ZD groups, pups in OZS group significantly decreased the time used for finding the platform and the swimming distance (p<0.05) and were similar to that of CO and PF groups (p>0.05). However, compared with ZD groups, pups in IZS did not show any improvement in the indexes of MWM (p>0.05) although their zinc serum concentration increased significantly (p<0.05). CONCLUSIONS: These results indicate that mild zinc deficiency during pregnancy and lactation leads to the impairment of learning and memory function in offspring, and that OZS, instead of intravenous transfusion zinc supplementation, can recover the impairment of spatial learning and memory function.

[Effect of penetrating needling at head acupoints on perennial allergic rhinitis].

OBJECTIVE: To evaluate the effects and safety of penetrating needling on head acupoints for perennial allergic rhinitis (PAR). METHODS: Eighty-one cases of PAR were randomly divided into an acupuncture group (41 cases) and a medication group (40 cases). Penetrating needling at head acupoints was adopted from Baihui (GV 20) to Qianding (GV 21) and from Shangxing (GV 23) to Shenting (GV 24) in the acupuncture group. A to tal 4-week treatment was given to the patients with 3 treatments a week. Loratadine tablet and azelastine hydrochloride nasal spray were given to the medication group continuously for 12 days. A follow-up was carried out 3 months after the treatment. The efficacy, symptom score and physical sign score, and side accidents were observed in both groups. RESULTS: The total effective rate was 95.1% (39/41) in the acupuncture group, which was better than 82.5% (33/40) in the medication group (P < 0.05). The total scores of clinical symptoms and each partial scores after the treatment, and total scores of clinical symptoms in follow-up were obviously decreased in both groups (all P < 0.01), the nasal obstruction score and the total scores of clinical symptoms in the acupuncture group were better than those in the medication group (P < 0.01, P < 0.05). Obvious side-effect had not been found during the treatment. CONCLUSION: Penetrating needling at head acupoints is a safe therapy for patients with PAR, and favorable effects can be found in both short term and long term.

Disruption of calmodulin-dependent protein kinase II α/brain-derived neurotrophic factor (α-CaMKII/BDNF) signalling is associated with zinc deficiency-induced impairments in cognitive and synaptic plasticity.

Maternal dietary Zn deficiency during fetal development induces substantial cognitive dysfunctions in the resultant offspring. The mechanism underlying this effect is unclear. The present study evaluated whether the impairments caused by gestational and lactational Zn deficiency are mediated by the hippocampal calmodulin-dependent protein kinase II α (α-CaMKII)/brain-derived neurotrophic factor (BDNF) signalling pathway as well as whether they can be restored by postnatal Zn supplementation. Rats were randomly divided into four groups on the first day of pregnancy (n 12): control (CO) group; pair-fed (PF) group; Zn-deprived (ZD) group; orally Zn-supplemented group. The spatial memory of the offspring was tested at postnatal day 35 using the Morris water maze. Long-term potentiation (LTP) in the rat hippocampal medial perforant path-dentate gyrus pathway was evaluated simultaneously, and α-CaMKII and BDNF protein levels were examined by Western blot analysis. The results demonstrated that the ZD group exhibited a significantly longer latency period in the Morris water maze as well as a significantly decreased LTP amplitude compared with the CO and PF groups. α-CaMKII and BDNF protein expression in the hippocampus was significantly reduced in the ZD group. Postnatal Zn supplementation restored the cognitive dysfunction induced by gestational Zn deficiency but could not completely reverse the decreased LTP and α-CaMKII/BDNF protein levels. Our findings suggest that the α-CaMKII/BDNF signalling pathway may be involved in Zn deficiency-induced cognitive and synaptic impairments.

Effects of maternal mild zinc deficiency and zinc supplementation in offspring on spatial memory and hippocampal neuronal ultrastructural changes.

OBJECTIVE: Knowledge about the hippocampal morphologic mechanisms of learning and memory for maternal mild zinc deficiency during pregnancy/lactation followed by zinc supplementation of pups after weaning is limited. This study examined the effects of zinc deficiency and zinc supplementation on cognition and hippocampal neurons. METHODS: One-day pregnant rats were randomly divided into four groups (n = 12): control (CO), pair-fed (PF), zinc-deprived (ZD), and oral zinc-supplemented (OZS). The CO and PF groups were fed a control diet (zinc 25 µg/g diet), and the others were fed a mildly zinc-deficient diet (zinc 2 µg/g diet) during pregnancy and lactation. After weaning (day 21), offspring in the OZS group were switched to a control diet. After 35 d, the behavioral function of the offspring was tested with the Morris water maze test. The ultrastructure of the hippocampal CA3 area was observed under a transmission electron microscope. RESULTS: Compared with the CO and PF groups, rats in the ZD group spent more time finding the latent platform and swam longer distances (P < 0.05). The time used finding the platform and the swimming distance in the OZS group were similar to those in the CO and PF groups (P > 0.05). In addition, apoptotic neuronal changes in the hippocampus were observed in the ZD group, whereas the reversal of neuronal morphologic changes was observed in the OZS group. CONCLUSION: The changes in hippocampal neuron morphology were consistent with the changes in the learning and memory ability of mildly zinc-deficient and zinc-supplemented offspring.

[Observation on therapeutic effect of acupuncture combined with medicine on mild cognition disorders in patients with post-stroke].

OBJECTIVE: To explore the curative effect and safety of acupuncture for mild cognitive disorders after stroke. METHODS: Randomized controlled trial was adopted and one hundred cases conforming to criteria were divided into a combined acupuncture and medication group (group A) and a medication group (group B), 50 cases in each group. The basic treatment of cerebrovascular disease was applied in two groups. The group A treated was with acupuncture at Baihui (GV 20), Shenting (GV 24) and Qucha (BL 4) etc. and oral administration of Nimodipine. In group B, Nimodipine was taken orally. The treatment lasted for 3 months, the scores of Mini-Mental State Examination (MMSE), modified Hasegawa Dementia Scale (HDS-R) and Barthel Index (BI) were observed before and after treatment in two groups. RESULTS: The total effective rate in group A was 66.7% (32/48), which was superior to 30.4% (14/46) in group B (P < 0.05). The scores of MMSE, HDS-R and BI after treatment were apparently improved as compared with those before treatment in two groups (all P < 0.01). The improvements in group A were superior to those in group B (all P < 0.05). There was no adverse event reported during the treatment in two groups. CONCLUSION: Acupuncture can improve activity of daily living and has significant effect in treating mild cognition disorders after stroke without adverse reactions.

[Clinical observation on therapeutic effect of three-step acupuncture for the secondary prevention of ischemic cerebral apoplexy].

OBJECTIVE: To observe the therapeutic effect and safety of three-step acupuncture for the secondary prevention of ischemic cerebral apoplexy. METHODS: One hundred and twenty cases of first-episode ischemic cerebral apoplexy were randomly divided into an observation group and a control group according to the visiting sequence, 60 cases in each group. Both groups were treated on the basis of the routine treatment, the observation group was treated with three-step acupuncture combined with oral administration of Aspirin for six months. The threestep acupuncture includs scalp acupuncture, body point acupuncture and rehabilitation training. The control group was treated with oral administration of Aspirin alone. Six-month follow-up was done in two groups. Then the recurrence rate of ischemic cerebral apoplexy, the improvement of neurologic impairment, activity of daily living and TCM symptom scores and the safety of three-step acupuncture between two groups were compared. RESULTS: The recurrence rate was 10.2% (5/49) in observation group, and 16.7% (9/54) in control group. There was no significant difference between two groups (P > 0.05). The observation group was superior to the control group in improving the scores of the neurologic impairment, activity of daily living and TCM symptom (P < 0.01, P < 0.001). There was no severe adverse reaction in two groups except 2 cases of gastrointestinal reaction caused by oral administration of Aspirin in control group. CONCLUSION: Three-step acupuncture has a certain therapeutic effect for both treatment and the secondary prevention of ischemic cerebral apoplexy, and it is one of the safe and effective methods for treating and preventing ischemic cerebral apoplexy in clinic.

[Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning].

OBJECTIVE: To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage. METHODS: Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope. RESULTS: Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved. CONCLUSION: DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.