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As one of the causes of exercise-induced fatigue, exercise-induced metabolic acidosis has attracted much attention. The effect of pyruvate supplementation on exercise-induced metabolic acidosis is rarely reported, and its mechanism has not been fully elucidated. Monocarboxylate transporters (MCTs) play an important role in the maintenance of the acid-base balance, but it is not clear whether pyruvate can alleviate acidosis by increasing the expression of MCTs. In this study, pyruvate (616 mg/kg/day) was supplemented to rats for one week, and then acute HIIE was performed. The HIIE protocol comprised 13 repeats of a 60 s sprint session at 110% VO
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Objective: To observe the effect of mild moxibustion on cancer-related fatigue, serum ghrelin and adiponectin in patients undergoing chemotherapy after colorectal cancer surgery. Methods: Seventy patients were divided into a control group and an observation group according to the random number table method, with 35 cases in each group. Patients in both groups were treated with conventional FOLFOX4 chemotherapy regimen. Patients in the control group also received routine treatments such as symptomatic treatment of complications, health education, nutritional support, and exercise intervention. Patients in the observation group received mild moxibustion on the basis of interventions used in the control group. The Piper fatigue scale-revision (PFS-R), Karnofsky performance status (KPS) and spleen and kidney yang deficiency syndrome were scored, and serum ghrelin and adiponectin levels were measured before and after treatment. Results: After treatment, total score of PFS-R in the control group did not change significantly (P>0.05), while in the observation group it was significantly reduced (P<0.05) and lower than that in the control group (P<0.05); KPS scores in both groups were increased (both P<0.05), and it was significantly higher in the observation group than in the control group (P<0.05); total score of spleen and kidney yang deficiency syndrome in the control group did not change significantly (P>0.05), while it was significantly reduced in the observation group (P<0.05) and lower than that in the control group (P<0.05); serum ghrelin and adiponectin levels in the control group had no significant changes (both P>0.05), but the levels were significantly increased in the observation group (both P<0.05) and higher than those in the control group (both P<0.05). Conclusion: Based on the routine treatments, mild moxibustion can relieve fatigue, improve quality of life, and improve the symptoms of spleen and kidney yang deficiency in patients undergoing chemotherapy after colorectal cancer surgery, which may be related to the regulation of serum ghrelin and adiponectin levels.
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Objective: To explore the mechanism of herbal cake-partitioned moxibustion in Crohn disease (CD) treatment by observing the effect of herbal cake-partitioned moxibustion on protein expressions of colonic M2 macrophage marker CD206, AMP-activated protein kinase (AMPK) and tuberous sclerosis complex (TSC) 2. Methods: Twenty-six specific pathogen free male rats were randomly divided into a normal group, a model group and a herbal cake-partitioned moxibustion group. The CD model was prepared by enema with the mixture of 5% (W/V) 2,4,6- trinitrobenzene sulfonic acid (TNBS) and 50% ethanol at 2:1 (volume ratio). After the model was successfully prepared, rats in the herbal cake-partitioned moxibustion group received herbal cake-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rat colon; immunohistochemical technique was used to detect the expression of colonic CD206 protein; Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) technologies were used to detect the protein and mRNA expressions of colonic AMPK and TSC2. Results: Compared with the normal group, rats in the model group showed damaged colonic mucosa, missing of the epithelial layer, thickened submucosa, vascular proliferation, massive infiltration of monocytes and lymphocytes, and cracked ulcers that reached the muscle layer. Rats in the herbal cake-partitioned moxibustion group showed reduced intestinal inflammation and healing intestinal epithelium ulcers. Compared with the normal group, rat colonic CD206 protein expression, and the protein and mRNA expressions of colonic AMPK and TSC2 were decreased in the model group (all P<0.01); compared with the model group, rat colonic CD206 protein expression was increased (P<0.01), as well as the protein and mRNA expressions of AMPK and TSC2 in the herbal cake-partitioned moxibustion (all P<0.05). Conclusion: Herbal cake-partitioned moxibustion can reduce intestinal inflammation in CD rats, increase colonic CD206 protein expression, and up-regulate the protein and mRNA expressions of colonic AMPK and TSC2.
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Objective: To explore the protective mechanism of acupuncture plus mild hypothermia for cerebral ischemia-reperfusion injury (CIRI) by observing the effects of acupuncture plus mild hypothermia on miRNA-204 and its target gene expressions in CIRI rat brain tissues. Methods: Sixty Sprague-Dawley rats were divided into a blank control group, a sham operation group, a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group according to the random number table method (n=10). Except for the blank control group and the sham operation group, rats in the other 4 groups received CIRI modeling. After the model was successfully established, rats in the blank control group were bred routinely for 72 h without any interventions; rats in the sham operation group and the model group were bred routinely for 72 h, and only received binding without other interventions after surgery; rats in the acupuncture group were bred routinely for 72 h, and received acupuncture at Dazhui (GV 14), Baihui (GV 20) and Shuigou (GV 26) after binding; rats in the mild hypothermia group were bred routinely for 72 h, and received mild hypothermia intervention for 72 h after binding; rats in the acupuncture plus mild hypothermia group were bred routinely for 72 h, followed by receiving acupuncture as in the acupuncture group and mild hypothermia therapy as in the mild hypothermia group after binding. The neurological impairment score, cerebral infarction area ratio, the expressions of miRNA-204 and its target genes including Map3k8, Ntrk2 and Ppp3r1 in the ischemic hippocampus of each group were observed after 72 h of intervention. Results: Before intervention, compared with the blank control group and the sham operation group, the neurological impairment scores and the infarction area ratios of the modelled rats were statistically significantly increased (all P<0.01), indicating that the model was successful. After intervention, compared with the model group, the neurological impairment scores of the three intervention groups were significantly reduced (all P<0.01); compared with the acupuncture group and the mild hypothermia group, the infarction area ratio in the acupuncture plus mild hypothermia group was significantly reduced (both P<0.01); compared with the model group, the three intervention groups showed significant inhibition of miRNA-204 expression in brain tissues (all P<0.05), which was most significant in the acupuncture plus mild hypothermia group (P<0.01); compared with the acupuncture group and the mild hypothermia group, the Map3k8 expression in the acupuncture plus mild hypothermia group was significantly increased (both P<0.01), but there were no significant differences in Ntrk2 and Ppp3r1 expressions between groups (all P>0.05). Conclusion: Acupuncture, mild hypothermia, and acupuncture plus mild hypothermia reduced the neurological impairment score and the cerebral infarction area in CIRI rats, while acupuncture plus mild hypothermia showed the most significant effect. In regulating miRNA-204 target gene expressions, acupuncture plus mild hypothermia showed the same effect on Ntrk2 and Ppp3r1 expressions, while better effect on Map3k8 expression compared with either acupuncture or hypothermia.
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Objective: To observe the effects of acupoints, cone numbers and durations of moxibustion with different moxibustion methods on skin surface and inside temperature, and to provide references for the clinical standardization of moxibustion amount. Methods: The 42 big-ear white rabbits were divided into 6 groups according to the random number table method, a 1-cone direct moxibustion group, a 2-cone direct moxibustion group, a 3-cone direct moxibustion group, a 1-cone herbal cake-partitioned moxibustion group, a 2-cone herbal cake-partitioned moxibustion group, and a 3-cone herbal cake-partitioned moxibustion group, with 7 rabbits in each group. Shenque (CV 8), Shenshu (BL 23) and Zusanli (ST 36) were used in each group, but the moxibustion methods, cone numbers and durations of moxibustion were different. Rabbits in each group received moxibustion once every other day for 5 times in total. During the intervention, a thermoelectricity coupled probe and a temperature recorder were used to record the real-time acupoint skin temperature and the temperature at different time points, so as to observe, analyze and process the real-time changes in the temperature difference between the surface and inside of acupoint skin. Results: For herbal cake-partitioned moxibustion, the best temperature for cone changing was (46.38±0.51) ℃ when the highest surface temperature was (49.20±0.52) ℃; the multi-factor comparison of acupoint × cone number × time and acupoint × moxibustion method × time showed that time × acupoint, time × moxibustion method and cone number × acupoint had interactive effects (all P<0.05). Comparing skin temperature differences between different cone numbers at the same acupoint, Shenque (CV 8) on the 1st and the 5th days, Shenshu (BL 23) on the 3rd and the 7th days, Zusanli (ST 36) on the 1st and the 9th days of experiment showed statistically significant differences (all P<0.05). The skin temperature comparison of different moxibustion methods at the same acupoint all had statistical differences (all P<0.05), except for Shenque (CV 8) before moxibustion, Shenshu (BL 23) before moxibustion and on the 5th day; Zusanli (ST 36) only showed statistical differences on the 5th and 7th days (both P<0.05). The skin temperature differences of different acupoints after moxibustion in the 1-cone, 2-cone and 3-cone groups were statistically different (all P<0.05); direct moxibustion and herbal cake-partitioned moxibustion at different acupoints were all statistically different (all P<0.05). Conclusion: Cone changing temperature under the same specifications of herbal cake-partitioned moxibustion was confirmed. Temperature difference between surface and inside of different acupoint skin at the same maximum temperature was significantly different due to the cone numbers and moxibustion methods, which showed the highest at Shenshu (BL 23), the second at Shenque (CV 8), and the lowest at Zusanli (ST 36). The influence of acupoint factor should be considered to determine the quantitative indicators of moxibustion.
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Objective: To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. Methods: A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. Results: After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P<0.05 or P<0.01), while the differences between the model group and the EA group were not statistically significant (all P>0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P<0.05), and the number of crossing the original platform tested by the MWM was significantly reduced (P<0.01), the protein and gene expressions of Bax and Caspase-3 were significantly increased (all P<0.001), the protein and gene expressions of Bcl-2 were significantly reduced (both P<0.001), and the number of neuron apoptosis was significantly increased (P<0.001) in the model group than in the normal group; the random blood glucose level was significantly reduced (P<0.05), the escape latency tested by MWM was significantly shortened (P<0.05), and the number of crossing the original platform tested by MWM was significantly increased (P<0.05), the protein and gene expressions of Bax and Caspase-3 were significantly reduced (all P<0.001), the protein and gene expressions of Bcl-2 were significantly increased (both P<0.001), and the number of neuron apoptosis was significantly reduced (P<0.001) in the EA group than in the model group. Conclusion: EA can improve the learning and memory damages induced by type 2 diabetic model rats with CI; the action mechanism may be achieved via anti-apoptosis.
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Objective: To observe the effects of electroacupuncture (EA) of different frequencies on transmission function, electromyography, nitric oxide synthase (NOS) content and interstitial cells of Cajal (ICC) expression of colon in rat models with slow transit constipation (STC). Methods: Of the 50 healthy male Wistar rats, 10 were randomly selected as a normal group and fed with ordinary diet, and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw) each day for continuous 120 d. The 40 successfully established STC rat models were randomly divided into a model group, a low-frequency EA group (2 Hz), a high-frequency EA group (100 Hz), and a variable-frequency EA group (2 Hz/100 Hz), with 10 rats in each group. Rats in the normal and the model groups were not given any treatment; the low-frequency EA and the high-frequency EA groups were given EA at Tianshu (ST 25), Zusanli (ST 36) and Zhigou (TE 6) with continuous wave at the designated frequency, and the variable-frequency EA group received sparse-dense wave (2 Hz/100 Hz) EA at the same acupoints, once a day for a total of 15 d. After treatment, the colonic transmission function, electromyography, NOS content and ICC expression (calculated by the difference in the area of the C-kit positive cells) of the rats in each group were measured. Results: For the colonic transmission function, compared with the normal group, the first black stool excretion durations of rats in the other groups were significantly prolonged (all P<0.05); compared with the model group, the first black stool excretion durations of rats in the three EA groups were significantly shortened (all P<0.05), which was significantly shorter in the variable-frequency EA group than in the low-frequency EA and high-frequency EA groups (both P<0.05). For the colonic electromyography, compared with the normal group, the amplitude was significantly increased and the frequency was accelerated in rats of the other groups (all P<0.05); compared with the model group, the amplitude was significantly reduced and the frequency was slowed down in the three EA groups (both P<0.05); compared with the low-frequency EA and the high-frequency EA groups, the amplitude was reduced and the frequency was significantly reduced in rats of the variable-frequency EA group (both P<0.05). Compared with the normal group, the colonic NOS contents were significantly increased in the other groups (all P<0.05); compared with the model group, the NOS contents were significantly reduced in the three EA groups (all P<0.05); compared with the low-frequency EA and the high-frequency EA groups, the content was significantly reduced in the variable-frequency EA group (all P<0.05). For the area of rat colonic C-kit-positive cells, compared with the normal group, the areas were significantly reduced in rats of other groups (all P<0.05); compared with the model group, the areas were increased significantly in the three EA groups (all P<0.05); compared with the low-frequency EA group, the area was increased significantly in the variable-frequency EA group (P<0.05). Conclusion: EA, especially EA at the 2 Hz/100 Hz variable-frequency, has a positive treatment effect on the STC model rats. It may improve rats' colonic function by regulating the electromyography, NOS content and ICC expression of colon.
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Objective: To explore the mechanism of An-pressing manipulation in improving post-stroke muscle spasticity, by observing the changes of γ-aminobutyric acid (GABA) and glycine (Gly) in plasma and gray matter of L1-L3 spinal cord anterior horn in post-stroke rats with muscle spasticity after An-pressing manipulation intervention. Methods: Ten of 80 adult male Sprague-Dawley (SD) rats were randomly selected as the blank group, and the remaining 70 were used for modeling. The middle cerebral artery occlusion (MCAO) rat model was established by insertion suture occlusion method in the left external carotid artery. Thirty rats with a Longa neurological score of 2-3 points and a modified Ashworth spasticity scale score of 1-, 1+, or 2 were included in the experiment. Using the random number table method, the 30 successfully modeled rats were randomly divided into a model group, an An-pressing tendon group and an An-pressing muscle belly group. Two days after modeling, rats in the An-pressing tendon group and An-pressing muscle belly group received An-pressing manipulation on the tendon and belly of quadriceps femoris muscle respectively, with the pressure of (350±50) g and the frequency of 5 s/time, 15 min per session, once a day for 5 continuous days. After the 5th treatment, the tension of the rat quadriceps femoris muscle was evaluated using the modified Ashworth spasticity scale. The Gly levels in rat plasma and L1-L3 segments of spinal cord were determined by enzyme-linked immunosorbent assay (ELISA). The GABA levels in rat plasma and L1-L3 segments of spinal cord were measured by high performance liquid chromatography (HPLC). Results: The decrease in rat muscle tension scored by the modified Ashworth spasticity scale in the An-pressing tendon group was more significant than that in the An-pressing muscle belly group (P<0.01); the increases in Gly and GABA levels in the rat plasma and L1-L3 segments of spinal cord were more significant in the An-pressing tendon group than those in the An-pressing muscle belly group (all P<0.01). Conclusion: Based on the theory of 'anti-stretch reflex' of tendon organs, the use of An-pressing manipulation to induce the 'anti-stretch reflex' by stimulating the tendon organs can improve the muscle spasticity of rats, which is better than An-pressing the muscle belly. Increased levels of Gly and GABA in rat plasma and L1-L3 segments of spinalcord may be one mechanism of An-pressing manipulation to improve muscle spasticity by stimulating tendon organs.
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Objective: To observe the effects of moxibustion on colonic inflammation, and the expressions of ubiquitin and nucleotide-binding oligomerization domain (Nod)-like receptor protein 3 (NLRP3) proteins in rats with ulcerative colitis (UC), and to explore the anti-inflammatory mechanism of moxibustion in the UC treatment. Methods: Clean grade male Sprague-Dawley (SD) rats were randomly divided into a normal group (NG), a model group (MG), a moxa-stick moxibustion group (MSMG) and a Western medicine group (WMG). UC model was prepared by freely drinking 35 g/L dextran sulfate sodium (DSS) solution. Bilateral Tianshu (ST 25) were selected for mild moxibustion treatment in the MSMG; mesalazine solution was intragastrically administrated in the WMG. Rats in the NG and MG were only grasped and fixed as in the MSMG without any treatment. After treatment, hematoxylin-eosin (HE) staining was performed to observe and score the colonic pathological damage under light microscope; immunofluorescence method was used to determine the expression of colonic ubiquitin protein; immunohistochemical method was used to detect the expressions of colonic interleukin (IL)-1β and NLRP3 proteins. Results: The colon tissue was severely injured, and the pathological score was significantly increased in the MG than in the NG (P<0.01), and the protein expressions of ubiquitin, NLRP3 and IL-1β in the colon were significantly increased (all P<0.01). Compared with the MG, the colonic damage was repaired, the inflammation and pathological scores were reduced, and the ubiquitin, NLRP3 and IL-1β protein expressions were decreased in the MSMG and WMG (all P<0.01). Correlation analysis revealed that the ubiquitin protein expression was correlated with the colonic pathological score and the NLRP3 protein expression (r=0.677, P<0.01; r=0.536, P<0.05). Conclusion: Moxibustion can down-regulate the protein expressions of ubiquitin, NLRP3 and IL-1β in the colon of UC rats, which may be one of the mechanisms to promote the repair of colonic inflammatory lesions and exert anti-inflammatory effects.
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OBJECTIVE@#To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models.@*METHODS@#PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review.@*RESULTS@#CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate.@*CONCLUSION@#CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.
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Animals , Mice , Drugs, Chinese Herbal , Therapeutic Uses , Osteosarcoma , Drug Therapy , Publication Bias , Risk Factors , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE@#To investigate the impact of Qing'e Pill (, QEP) on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.@*METHODS@#Ninety-six 8-week-old specific pathogen free C57BL/6 mice were randomly divided into 4 groups (24/group): sham, ovariectomised osteoporosis model, oestradiol-treated, and QEP-treated groups. Three months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional (3D) parameters of their cancellous bone microstructure. The impact of ovariectomy, the effect of oestradiol and QEP intervention on cancellous bone microstructure, and the expression of β-catenin were evaluated.@*RESULTS@#The oestradioland the QEP-treated groups exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickneßs, bone surface to bone volume ratio (BS/BV), and β-catenin expression compared with those of the model group (P <0.05). In contrast, the structure model index, trabecular separation, and BS/BV were significantly decreased compared with those of the ovariectomised osteoporosis model group (P <0.05). No differences were observed in the above parameters between animals of the QEP- and oestradiol-treated groups.@*CONCLUSIONS@#The increased β-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice. Our findings provide a scientific rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
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Objective: To compare the risk angle and safety angle of needling Yamen (GV 15) between the atlanto-axial dislocation (AAD) patients and healthy subjects. Methods: A total of 177 AAD patients diagnosed and treated at the Center of Upper Cervical Vertebra of Beijing China-Japan Friendship Hospital between January 2010 and January 2018 were included in the AAD group. Another 207 healthy subjects were included in the normal group. There were totally 191 males and 193 females. The MRI scan was performed for the cervical vertebrae to measure the risk angle and safety angle of acupuncture at Yamen (GV 15) on the sagittal image. Results: In the AAD group, the risk angle was (13.14±3.99)° and the relative safety angle was (10.31±3.23)° for the perpendicular needling, while the oblique needling risk angle was (9.09±3.09)° for the male; the risk angle was (12.12±2.74)° and the relative safety angle was (10.56±2.09)° for the perpendicular needling, while the oblique needling risk angle was (9.70±2.95)° for the female. In the normal group, the risk angle was (7.89±1.59)° and the relative safety angle was (10.21±3.55)° for the perpendicular needling, while the oblique needling risk angle was (16.07±1.77)° for the male; the risk angle was (6.93±1.45)° and the relative safety angle was (10.70±2.94)° for the perpendicular needling, while the oblique needling risk angle was (14.89±2.18)° for the female. The perpendicular needling risk angles for the males and females in the AAD group were larger than those in the normal group, and the differences were statistically significant (bothP<0.01); for the inner-group comparison, there was no significant difference in the perpendicular needling risk angle between the male and the female in the AAD group (P>0.05); however, the perpendicular needling risk angle for the male was larger than the female, and the difference was statistically significant in the normal group (P<0.01). There were no significant differences in the relative safety angle for both the male and the female between the AAD group and the normal group (bothP>0.05). For the inner-group comparison, there was no significant difference in the relative safety angle between the male and the female (P>0.05). The oblique needling risk angles for both the males and females were smaller in the AAD group than those in the normal group, and the differences were statistically significant (bothP<0.01); the oblique needling risk angle for the male was not significantly different from that for the female in the AAD group (P>0.05); in the normal group, the oblique needling risk angle for the male was larger than that for the female, and the difference was statistically significant (P<0.01). Conclusion: Under the AAD condition, the risk angle and safety angle of acupuncture at Yamen (GV 15) change significantly, perpendicular needling should be better if performed slightly lower than the horizontal direction, and the oblique needling should be safer across the occipital foramen toward the occipital bone.
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Objective:To explore the optimal thermal effect parameter combination of An-pressing manipulation based on the pressing force, time and frequency, and to compare the thermal effect differences between the rhythmic and the continuous An-pressing manipulations. Methods:Three levels of light, moderate and heavy pressing forces were determined according to the An-pressing forces of the clinical tuina physicians; the pressing time and frequency parameters were determined according to the literatures about An-pressing manipulation. The volunteers were stimulated by the homemade An-pressing manipulation stimulator on the right Xinshu (BL 15), and then the three-factor and three-level orthogonal tests were carried out according to the test sequence specified by the L9(34) orthogonal table, and the temperature before and after pressing was recorded by an infrared thermal imaging system to screen the best parameters for the thermal effect of the An-pressing manipulation, thus to determine the optimal pressing parameters. The optimal parameters were then used for both continuous and rhythmic An-pressing manipulations to stimulate the bilateral Xinshu (BL 15). The temperature changes after pressing and the duration of the thermal effect (temperature difference ≤0.5℃ on both sides) were recorded by the infrared thermal imaging system, to explore the differences in the thermal effects of different An-pressing manipulations. Results:Among the three factors of pressing force, time and frequency, the influences of different pressing forces on temperature were significantly different (F=32.843,P=0.030), and the influence of 2.5 kg pressing force was the most significant; the effects of different pressing time on temperature were significantly different (F=54.102,P=0.018), and the pressing time of 7.5 min was the most significant; the influences of different pressing frequencies on temperature were not statistically significant (F=2.181,P=0.314), though the influence of 10 times/min pressing frequency was the largest. The influences on temperature difference of the rhythmic and the continuous An-pressing manipulations were significantly different (P=0.031 on the left side andP=0.045 on the right side), but there was no statistical difference in the duration of the thermal effect (P=0.690). Conclusion:The An-pressing manipulation parameters that significantly affect the temperature difference are pressing force and time. The optimal combination of thermal effect parameters is pressing force of 2.5 kg, time of 7.5 min, and frequency of 10 times/min. The local thermal effect of the rhythmic An-pressing manipulation is significantly greater than of the continuous An-pressing manipulation.
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Objective:To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Methods:Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the blank group, the body weight of the model group decreased significantly after modeling (P<0.05); compared with the model group, the rats in the moxibustion group had increased body weight during the middle and late stages (bothP<0.05). The tumor volumes of rats in the moxibustion group and the infrared group were smaller than the volume in the model group (bothP<0.05). The tumor growth inhibition rate in the moxibustion group was significantly higher than that in the infrared group (P<0.05). The case number of tumor metastasis in the moxibustion group was smaller than that in the model group and the infrared group. The VEGF level in the tumor tissues of the model group was statistically significantly higher than that in the blank group (P<0.05). Compared with the model group, the VEGF levels in the moxibustion group and the infrared group were statistically significantly lower (bothP<0.05). The EGF levels in the tumor tissues of the model group was statistically significantly lower than that in the blank group (P<0.05); compared with the model group, the EGF levels in the moxibustion group and the infrared group were statistically significantly increased (bothP<0.05). Conclusion:Moxibustion can increase the body weight, inhibit the tumor growth, invasion and metastasis in gastric tumor-bearing rats, which may be related to the regulation of VEGF and EGF expressions in tumor tissues.
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Objective:To observe the effect of moxibustion on T lymphocyte subsets in peripheral blood of rats with gastric cancer. Methods:Sixty healthy Sprague-Dawley (SD) rats were adaptively fed for one week. By the random number table method, 10 rats were randomly selected as a blank group, and 12 rats were randomly selected to simulate the tumor transplantation process; after transplantation, 10 rats were randomly selected as a sham operation group. The remaining 38 rats were used to prepare gastric cancer models by gastric transplantation of the Walker-256 tumor tissue; 8 rats were randomly selected to verify the successful modeling after 7 d; the remaining 30 rats were randomly divided into a model group, a moxibustion group and an infrared group by the random number table method, with 10 rats in each group. From the first day of enrollment, the rats in the moxibustion group received mild moxibustion at Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) (the first group) and bilateral Pishu (BL 20) and Weishu (BL 21) (the second group), and the two groups of acupoints were alternated every other day. The rats in the infrared group received infrared radiation on the stomach area and the area on the back between the T12-T13 spinous processes, the two areas were alternated every other day. Rats in the moxibustion group and the infrared group were treated for 20 min each time, once a day for 21 d. Rats in the blank group, the sham operation group, and the model group were simultaneously grasped and fixed, and no other treatment was performed. After 21 d of intervention, the rats in each group were fasted for 12 h, and blood was collected from the orbits. The numbers of CD3+, CD3+CD4+, CD3+CD8+ T lymphocytes in peripheral blood were determined by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. The rats were sacrificed and the thymus was dissected under sterile conditions to calculate the thymus index. Results:Compared with the blank group, the thymus index, peripheral blood CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ ratio in the sham operation group did not change significantly (allP>0.05). Compared with the blank group, the thymus index of the model group was increased (P<0.05), the CD3+ and CD3+CD8+ T lymphocytes were increased (bothP<0.01), and the CD3+CD4+/CD3+CD8+ ratio was decreased (P<0.05). Compared with the model group, the thymus index of the moxibustion group was increased (P<0.01), and CD3+, CD3+CD4+ and CD3+CD8+ T lymphocytes and the ratio of CD3+CD4+/CD3+CD8+ in peripheral blood were increased (allP<0.05). Compared with the infrared group, the thymus index of the moxibustion group was significantly increased (P<0.05), the CD3+ and CD3+CD4+ T lymphocytes in the peripheral blood were significantly increased (bothP<0.01), and the CD3+CD8+ was increased (P<0.05). Conclusion:Moxibustion can significantly increase the thymus index of gastric cancer-bearing rats and activate CD3+CD4+ and CD3+CD8+ T lymphocytes in peripheral blood.
ABSTRACT
Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.
Subject(s)
Humans , Chromosome Aberrations , Chromosome Disorders , Cytogenetic Analysis , Multiple Myeloma , Prognosis , Retrospective StudiesABSTRACT
Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.
Subject(s)
Humans , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 17 , Multiple Myeloma , Neoplasm Staging , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.
Subject(s)
Humans , Bortezomib/therapeutic use , Multiple Myeloma/therapy , Neoplasm Recurrence, Local , Neoplasm, Residual/diagnosis , Prognosis , Risk Assessment , Treatment OutcomeABSTRACT
<p><b>Background</b>Outflow tract (OFT) septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart.</p><p><b>Methods</b>Serial sections of 27 human embryonic hearts from Carnegie stage (CS) 10 to CS19 were immunohistochemically stained with antibodies against α-smooth muscle actin (α-SMA) and myosin heavy chain.</p><p><b>Results</b>At CS10-CS11, the OFT wall was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT.</p><p><b>Conclusions</b>Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopulmonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT.</p>
Subject(s)
Humans , Actins , Metabolism , Alkaline Phosphatase , Metabolism , Aorta , Embryology , Heart , Embryology , Heart Valves , Embryology , Immunohistochemistry , Myosin Heavy Chains , MetabolismABSTRACT
Objective: To observe the effects of different doses of ginger-partitioned moxibustion on serum trefoil factor 1 (TFF1) and mucin 5AC (MUC5AC) levels, as well as the expression of epidermal growth factor receptor (EGFR) in gastric mucosa of rats with spleen deficiency syndrome, therefore, to explore the possible mechanism and the dose-effect characteristics of ginger-partitioned moxibustion in spleen deficiency syndrome. Methods: Seventy-five SPF grade Sprague-Dawley (SD) rats were randomly divided into a blank control group (group A), a model group (group B), a 3 moxa-cone ginger-partitioned moxibustion group (group C1), a 6 moxa-cone ginger-partitioned moxibustion group (group C2) and a 9 moxa-cone ginger-partitioned moxibustion group (group C3) using random number table method, 15 rats in each group. Except group A, rats in the other groups received intragastric administration of 4 ℃200% concentrated Da Huang (Radix et Rhizoma Rhei) to prepare spleen deficiency syndrome model. After successful modeling, rats in group B received no treatment; rats in group C1, C2 and C3 were treated with 3, 6 and 9 moxa-cone ginger-partitioned moxibustion at Zusanli (ST 36) and Zhongwan (CV 12) respectively for 8 continuous days. The general symptom score of rats was observed. The serum levels of TFF1 and MUC5AC were detected by enzyme-linked immunosorbent assay (ELISA). The expression of EGFR protein in gastric mucosa was detected by immunohistochemistry. Results: After the treatment, compared with group A, the spleen deficiency symptom score was increased in group B, the levels of serum TFF1 and MUC5AC, the EGFR protein expression in gastric tissues of group C1, C2 and C3 were significantly increased (all P<0.01); compared with group B, the spleen deficiency scores were decreased in group C1, C2 and C3, and the serum levels of TFF1 and MUC5AC, as well as EGFR protein expression in gastric tissues were increased (all P<0.01). Compared with group C1, the spleen deficiency scores were decreased in group C2 and C3, the serum levels of TFF1 and MUC5AC, and the expression of EGFR protein in gastric tissues were increased (all P<0.01), however, there was no significant difference between group C2 and C3 (all P>0.05). The mechanism may be related to the increase of serum TFF1 and MUC5AC levels and activation of EGFR protein. Conclusion: Ginger-partitioned moxibustion can improve the symptoms, as well as promote the proliferation and repair of gastric mucosa in rats with spleen deficiency. The therapeutic efficacy of 6 or 9 moxa-cone ginger-partitioned moxibustion is better than that of 3 moxa-cone ginger-partitioned moxibustion, while the efficacies are equivalent between 6 and 9 moxa-cone ginger-partitioned moxibustion groups.