Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise.@*METHODS@#A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated.@*RESULTS@#After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01).@*CONCLUSION@#Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Technical recommendations for pragmatic randomized controlled trials of heat-sensitive moxibustion in community (Ⅱ): organization, implementation and follow-up visits / 中国针灸

Based on the community research experience of heat-sensitive moxibustion, this study explained technical recommendations for pragmatic randomized controlled trials (pRCTs) of heat-sensitive moxibustion in community from 7 aspects: selection of community research sites, ethical approval and registration, patient recruitment, training of standard operating procedures, ensuring patient compliance, quality control of follow-up visits and patient safety, which aimed to reduce the difficulty of research execution and improve the quality of pRCTs implementation and follow-up visits of heat-sensitive moxibustion.

Technical recommendation for pragmatic randomized controlled trial of heat-sensitive moxibustion in community (Ⅰ): randomization with consideration of patient preference / 中国针灸

Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.

Development and maturation of intestinal organoids in neonatal mice / 中华围产医学杂志

Objective:To investigate the development and maturation process of intestinal organoids in neonatal mice so as to provide a new model for research on perinatal/neonatal intestinal epithelial development and related diseases.Methods:Intestinal tissue of 3-day-old C57BL/6 mice were collected and cultured for mouse intestinal organoids (MIOs) under standard conditions down to the fifth generation. The morphological changes of MIOs were observed and recorded using inverted phase contrast microscope. Real-time fluorescent quantitative polymerase chain reaction and immunofluorescence technique were used to detect the expression and location of markers of intestinal stem cells and differentiated cells of intestinal epithelium among different generations of MIOs (Selected marker genes: Lgr5 for intestinal stem cells, Tpm2 and Gja1 for fetal intestinal progenitor cells, Villin for intestinal epithelial cells, Lyz1 for Paneth cells, Muc2 for goblet cells, Chga for endocrine cells; Selected marker proteins: villin for intestinal epithelial cells, mucin 2 for goblet cells, chromaffin A for endocrine cells, lysozyme for Paneth cells). One-way analysis of variance and Bonferroni test were adopted for statistical analysis. Results:Two types of MIOs were observed, immature spheroid and mature organoids with crypt-villus structure. Spheroid was the main form in the primary culture. From primary to the second generation, the proportion of spheroids decreased from (96.61±1.36)% to (8.93±1.50)%, and so did the size ( F=12.88, P<0.001). During the second to the fifth generation, mature organoid, as the main form, increased from (91.07±1.50)% to (95.56±2.14)%. The expression of intestinal stem cell marker Lgr5 in the second generation decreased to 0.40±0.06 times of the primary one ( F=76.75, P<0.001) and then increased after this period. The expression of fetal intestinal progenitor markers Tpm2 decreased significantly during the passage (primary generation: 1.00±0.11, the fifth generation: 0.003±0.001, F=148.00, P<0.001); And the expression of Gja1 decreased from primary generation (1.00±0.14) to the second generation (0.06±0.04) ( F=197.10, P<0.001), but kept stable from the second to fifth genetation ( F=2.20, P=0.13). The expressions of gene markers of differentiated cells in intestinal epithelium, including enterocytes, goblet cells, endocrine cells, and Paneth cells, increased after the second generation (the second generation: Villin: 0.46±0.11; Muc2: 0.68±0.29; Chga: 2.53±0.16; Lyz1: 0.98±0.21; the fifth generation: Villin: 1.02±0.05; Muc2: 8.79±0.61; Chga: 4.32±0.45; Lyz1:3.81±0.36; all P<0.05). Immunofluorescence showed that villin, the intestinal epithelial cell marker protein, was distributed along the villus-side of MIOs in primary and the fifth generation culture. Mucin 2 from goblet cell and chromaffin A from endocrine cell expressed at a very low level in the primary generation, while higher in the fifth generation. In the primary culture, lysozyme from Paneth cell was evenly distributed in organoid cells, and high fluorescent dot-shaped expression was observed in the fifth generation. Conclusions:The development and maturation of immature intestinal epithelium can be simulated by continuous culture of neonatal MIOs. MIOs between the primary and second generation could be used as a research model for development of perinatal intestinal epithelium, and the second to the fifth generation as a model for neonatal intestinal diseases studies.

Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area.@*METHODS@#A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining.@*RESULTS@#Compared with the sham-operation group, EF and FS were decreased (@*CONCLUSION@#Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

Effect of electroacupuncture on expression of IL-23/IL-17 axis and TLR4 in infarcted tissue in rats with myocardial infarction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury.@*METHODS@#Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot.@*RESULTS@#Compared with the sham-operation group, the EF was decreased (@*CONCLUSION@#EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.

Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine / 中国中药杂志

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

Total flavonoids of bugloss limits left ventricular remodeling after myocardial infarction in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.

Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine / 中国中药杂志

Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA （mtDNA）and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide（NMN）and FOXO4-DRI,a peptide of anti-aging. In addition,there are many new discoveries in the field of plant extracts,in which,the extracts from Chinese herbal medicine（CHM）,some single CHMs and the classical prescriptions of CHM,represented by curcumin and resveratrol,have the partial anti-aging effects by regulating the molecular mechanisms of aging both in vivo and in vitro. In brief,developing or exploring anti-aging drugs,especially the natural drugs,is one of the main development directions in the field of anti-aging research in the basis of the molecular regulative mechanisms of aging.

Clinical observation on acupotomy for treatment of simple obesity / 中国针灸

<p><b>OBJECTIVE</b>To compare the efficacy differences among acupotomy, electroacupuncture and acupuncture for treatment of simple obesity.</p><p><b>METHODS</b>One hundred and five cases were randomly divided into an acupotomy group, an electroacupuncture group and an acupuncture group, 35 cases in each group, and Zhongwan (CV 12), Tianshu (ST 25), Shangjuxu (ST 37), Sanyinjiao (SP 6), etc, were selected in three groups and also with selection of acupoints according to symptoms. The acupotomy group was treated with acupotomy 40 mm in length and 0.6 mm in diameter, the electroacupuncture group with the Han's LH402A electroacupuncture stimulator and the acupuncture group with simple acupuncture treatment. The clinical therapeutic effects of three groups were compared. The obesity signs such as body weight, body mass index (BMI), obesity degree, etc., and blood lipid and fasting blood sugar (FBS) were observed.</p><p><b>RESULTS</b>The markedly effective rate of 91.4% (32/35) in the acupotomy group was higher than that of 71.5% (25/35) in the electroacupuncture group and that of 42.9% (15/35) in the hand acupuncture group (both P<0.05). There were significant differences in the obesity signs and blood fat and FBS of the three groups before and after treatment (P<0.05, P<0.01). The differences rates of body weight, BMI, obesity degree, chest circumference, waistline, thighline, waist-hip ratio, total cholesterol before and after treatment in the acupotomy group were all better than those in the electroacupuncture group and in the acupuncture group (all P<0.05), and the differences rates of hipline, FBS in the acupotomy group were better than those in the acupuncture group (both P<0.001).</p><p><b>CONCLUSION</b>Acupotomy treatment can obviously reduce fat, FBS and blood lipid and has obvious therapeutic effects on simple obesity.</p>

Randomized controlled trials on the influence and mechanism of manipulation on delayed onset muscle soreness after eccentric exercise / 中国骨伤

<p><b>OBJECTIVE</b>To observe and compare the influence of pre- and post-exercise manipulation and natural recovery without any intervention on delayed onset muscle soreness (DOMS) after eccentric exercise and to explore the manipulation therapeutic mechanism on the metabolism of oxygen free radical (OFR).</p><p><b>METHODS</b>The study was carried on during Apr. to Jul. in 2008 at Nanjing University of TCM. The 30 healthy male students were divided into 3 groups randomly according to condition-equivalence principle including control group (C), pre-exercise manipulation group (A), post-exercise manipulation group (B). Before exercise, group A were intervened by manipulation for 30 minutes, which was followed by exercise 5 minutes later. While 30 minutes after exercise, group B accepted manipulation for 30 minutes and continued manipulation once a day for consecutive 3 days. Group C were not intervened by any approaches before or after exercise. The clinical manifestations, which include soreness intensity and lasting time, maximal isometric strength, arm girth, elbow range of motion, were evaluated at the 1st hour before exercise, immediately, 24th, 48th and 72th hours after exercise. Meanwhile, serum creatine kinase (CK), serum superoxide dismutase (SOD), serum malonaldehyde (MDA) were determined at the 1st hour before exercise, immediately, 24th and 48th hours after exercise.</p><p><b>RESULTS</b>Compared to group C, group A and B were manifested by significantly lower peak soreness (P < 0.01, P < 0.05), significantly better recovery of elbow flexing degree at the 72th hour after exercise (P < 0.05) and significantly lower rising range of serum CK at the 48th hour after exercise (P < 0.01). Comparing to group C, group A was manifested by significantly shorter lasting time of muscle soreness (P < 0.01) and significantly better recovery of maximal isometric strength of the 72th hour after exercise (P < 0.01). Compared to group C, group B was manifested by significantly better recovery of elbow extending degree at the 72 th hour after exercise (P < 0.01). There was no significant difference in the change of arm girth among the three groups. The level of Serum SOD, MDA and SOD/MDA at the 48th hour after exercise in group A and B were significantly different from those in group C (P < 0.01, P < 0.01, P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Through improving the metabolism of OFR, pre-exercise and post-exercise manipulation can partially prevent and treat DOMS respectively. In addition, preventive effect by pre-exercise manipulation is better than curing effect by post-exercise manipulation, which proves the TCM thought, that is, prevention superior to treatment.</p>