Explaining how childhood physical abuse and physical neglect influence adult depression: An analysis with multiple sequential mediators.

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.

In vivo evaluation of liver function by multimodal imaging in an alcohol-induced liver injury model.

Background: Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in vivo in experimental studies. In this study, we established a multimodal imaging approach for in vivo liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research. Methods: In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by in vivo confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured. Results: In vivo multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice. Conclusions: Utilizing in vivo multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.

[Modified acupuncture at sphenopalatine ganglion for allergic rhinitis: a randomized controlled trial].

OBJECTIVE: To observe the effect of modified acupuncture at sphenopalatine ganglion for allergic rhinitis (AR). METHODS: A total of 80 patients with AR were randomly divided into an observation group and a control group, 40 cases in each group. In the observation group, modified acupuncture at sphenopalatine ganglion was given, 30 min each time, 2 times a week and with an interval of 3-4 days. In the control group, budesonide nasal spray was given. Both groups were treated for 4 weeks. The total nasal symptom score (TNSS) and total non-nasal symptom score (TNNSS) were observed before treatment, after first treatment, after last treatment and 4 weeks after treatment; the scores of visual analogue scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were observed before treatment, after last treatment and 4 weeks after treatment; the recurrence condition was evaluated 4 weeks after treatment; the clinical efficacy was evaluated after last treatment in the two groups. RESULTS: Compared with before treatment, the total scores and each score of TNSS, TNNSS scores after first treatment, after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01, P<0.05). After first treatment, the total score, stuffy nose score, itchy nose score of TNSS and TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). After last treatment, the total score, stuffy nose score, itchy nose score of TNSS in the observation group were lower than the control group (P<0.01). Four weeks after treatment, the total score and each score of TNSS, TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). Compared with before treatment, the scores of VAS and RQLQ after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). The recurrence rate was 13.5% (5/37) in the observation group, which was lower than 44.8% (13/29) in the control group (P<0.01). The total effective rate was 92.5% (37/40) in the observation group, which was higher than 72.5% (29/40) in the control group (P<0.05). CONCLUSION: Modified acupuncture at sphenopalatine ganglion could effectively improve symptoms and quality of life in patients with AR, and the recurrence rate is lower.

Effects of electroacupuncture on liver function in mice with chronic alcoholic liver injury: visual display by in vivo fluorescence imaging.

OBJECTIVE: Acupuncture can improve the symptoms of alcohol-induced bodily injury and has been accepted by the World Health Organization. In this study, in vivo fluorescence imaging (IVFI) was applied to display and evaluate the effect of electroacupuncture (EA) on liver function (LF) in mice with chronic alcoholic liver injury (cALI). METHODS: IVFI of the Cy5.5-galactosylated polylysine (Cy5.5-GP) probe targeting the liver asialoglycoprotein receptor (ASGPR) and liver indocyanine green (ICG) clearance was performed to visually evaluate the effect of EA at ST36 and BL18 on liver reserve function and hepatic metabolism in mice with cALI. In addition, changes in ASGPR expression, serum indexes of LF, and hepatic morphology were observed. RESULTS: After EA at ST36 and BL18, the ASGPR-targeted fluorescence signals (FS) in the liver increased significantly in cALI mice (p < 0.05) and exhibited relationships with liver ASGPR expression, liver ICG clearance, liver histology, and serum marker levels of LF in cALI mice undergoing EA intervention. CONCLUSIONS: As displayed by IVFI, EA at ST36 and BL18 appears to improve liver reserve function and inhibit the development of liver injury in mice with cALI. EA may have potential as a treatment strategy to protect against ALI.

New Sorbicillinoids with Tea Pathogenic Fungus Inhibitory Effect from Marine-Derived Fungus Hypocrea jecorina H8.

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 µM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.

[Effect of Bo's abdominal acupuncture as adjunctive therapy on rheumatoid arthritis and ESR, RF and CRP levels].

OBJECTIVE: To explore the therapeutic effect on rheumatoid arthritis treated with Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" and the relevant effect mechanism. METHODS: A total of 104 patients with rheumatoid arthritis were randomized into and an observation group (52 cases, 1 case dropped off) and a control group (52 cases, 3 cases dropped off). In the control group, methotrexate tablets were prescribed for oral administration, 5 mg each time, once a week. In the observation group, on the base of the treatment as the control group, Bo's abdominal acupuncture was combined. The acupoints included Zhongwan (CV 12), Xiawan (CV 10), Guanyuan (CV 4), Qihai (CV 6), Huaroumen (ST 24), Wailing (ST 26), etc. The treatment was given once every two days, 3 times weekly. Totally 12 weeks were required in the two groups. Before and after treatment, the score of TCM symptoms (including joint pain, the range of motion, joint swelling and morning stiffness), and the levels of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and C-reactive protein (CRP) were observed and the clinical therapeutic effect was assessed in the two groups. RESULTS: After treatment, the total effective rate was 88.2% (45/51) in the observation group, higher than 73.5% (36/49) in the control group (P<0.05). The score of each TCM symptom and the total scores after treatment were all lower than those before treatment in the two groups (P<0.05), and these scores in the observation group were lower than the control group (P<0.05). After treatment, the levels of ESR, RF and CRP were all lower than those before treatment in the two groups (P<0.05), while the levels of those indexes in the observation group were lower than the control group (P<0.05). CONCLUSION: Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" as the adjunctive therapy effectively relieves the clinical symptoms in the patients with rheumatoid arthritis, which is related to the reduction of ESR, RF and CRP in mechanism.

Over-expression of SRD5A3 and its prognostic significance in breast cancer.

OBJECTIVE: The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. METHODS: We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. RESULTS: Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). CONCLUSIONS: SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.

[Analysis on the route of conception vessel and governor vessel in Huangdi Neijing (The Yellow Emperor's Inner Classic)].

On the base of the analysis on the original text in Huangdi Neijing (The Yellow Emperor ¢s Inner Classic) and in association with the meridian tracing experiment results in transparent fish, rats and human body, the routes of conception vessel and governor vessel were recognized de novo. The starting site of conception vessel has been described as "the center of uterus" and "the inferior part of Zhongji (CV 3)", which refer to the same region. The running course of conception vessel includes 3 routes, named the deep abdominal route, the deep dorsal route and the superficial abdominal route. The governor vessel starts at Qugu (CV 2) on the pubis and its running course includes 4 routes, named the buttock-spine ascending route, the head-back descending route, the abdomen-face ascending route and the head-back midline route. Both the conception vessel and the governor vessel distribute on the anterior and the posterior aspects of the trunk, head and face, but they are in deep and shallow layers respectively, forming two cycles internally and externally. Such recognition is really not the pattern, known by the people, that conception vessel distributes in the front, while the governor vessel on the back.

[Sixty years of meridian-collateral exploration: a road of interdisciplinary research].

The theory of traditional Chinese medicine believes that meridian-collateral (jingluo) is an important system to maintain life and participates in the formation and cure of disease. Exploring the biological connotation of meridian-collateral is the key content in the modern research of traditional Chinese meridian. For more than 60 years, scholars at home and abroad have carried out the researches of meridian-collateral from the fields of biomedicine (e.g. physiology, anatomy and histomorphology), imaging, physics, chemistry, computer technology, etc. Meridian-collateral research in modern times demonstrates a multi-disciplinary historical development and provides multi-perspective scientific information for understanding meridian-collateral. The meridian-collateral research in future needs more accurate multidisciplinary intersection, which will be the light of hope to reveal the biological connotation of meridian-collateral.

[Effect of electroacupuncture on the hemorheology and hepatic microcirculation in mice with chronic alcoholic liver injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the hemorheology and hepatic microcirculation in mice with chronic alcoholic liver injury (cALI), so as to explore the microcirculation mechanism of EA underlying regulating liver function in cALI mice. METHODS: Forty Kunming mice were randomly assigned to control, model, acupoint EA and non-acupoint EA groups, with 10 mice in each group. The cALI model was established by gavage with 50% ethanol (15 mL/kg，2 times per day with 8 hours' interval) for 28 d. Mice in the acupoint EA group received EA at bilateral "Zusanli" (ST36) and "Ganshu"(GB11) for 20 min, once daily for 14 d. And mice in the non-acupoint EA group received EA the spot about 1 cm lateral to GB11 and 0.5 cm lateral to ST36 respectively for 20 min, once daily for 14 d. The hepatic blood perfusion (HBP) of mice was detected by laser speckle perfusion imaging. The index of hemorheology, serum markers of liver function and hepatic histology in mice were observed by automatic blood rheometer, automatic bio-analysis machine and H.E. staining, respectively. RESULTS: Compared with the control group, the HBP of the model group was significantly decreased (P<0.05); the low-cut whole blood viscosity, plasma viscosity, and erythrocyte sedimentation level were significantly increased （P<0.05）, and the red blood cell deformation index was significantly decreased (P<0.05); serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) increased significantly (P<0.05) in the model group. Hepatocyte steatosis accompanied by inflammatory cell infiltration and focal necrosis was observed in the model group. After EA at ST36 and GB11, and in comparison with the model group showed that the HBP was significantly increased (P<0.05); the low-cut whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate and serum GGT were significantly decreased (P<0.05), and the red blood cell deformation index was significantly increased (P<0.05）; the degree of fatty degeneration in the liver tissue was reduced, and the focal necrosis was reduced. The plasma viscosity, erythrocyte sedimentation rate were significantly decreased (P<0.05), and the red blood cell deformation index was significantly increased in the non-acupoint EA group relevant to the model group (P<0.05). The erythrocyte sedimentation rate and the red blood cell deformation index of the acupoint EA group was significantly lower than that of the non-acupoint EA group (P<0.05). CONCLUSION: EA at ST36 and GB11 could improve the hemorheological disorder and the hepatic microcirculation, and inhibit the deve-lopment of liver injury in cALI mice.

[Analysis on the defensive function of defensive qi in Huangdi Neijing (The Yellow Emperor's Inner Classic)].

The defensive function of defensive qi in Huangdi Neijing (The Yellow Emperor 's Inner Classic) includes the effect of immune system of human body against the pathogen invasion. According to the basic research, it is believed that the circulation of defensive qi in meridian is interpreted as the flow of interstitial fluid in the low hydraulic resistance channel that is overlapped with lymphatic vessels, transporting the antigen information from interstitium to lymph nodes and generating adaptive immune response. Enhancing meridian circulation and promoting the flow of interstitial fluid may improve the immunity, which demonstrating the thought of traditional Chinese meridian as "pathogens failing to invade the body when the anti-pathogenic qi is strong enough inside".

In Vivo Visualization of the Pericardium Meridian with Fluorescent Dyes.

The anatomical basis of acupuncture meridians continues to be enigmatic. Although much attention has been placed on potential correlations with inter/intramuscular fascia or lower electrical impedance, animal studies performed in the past 40 years have shown that tracer dyes-specifically Tc-99m pertechnetate-injected at strategic skin points generate linear migrations closely aligning with acupuncture meridians. To evaluate whether this phenomenon is also observable in humans, we injected two fluorescent dyes-fluorescein sodium and indocyanine green (ICG)-into the dermal layer both at acupuncture points (PC5, PC6, and PC7) and a nonacupoint control. Fifteen healthy volunteers were enrolled in this study. Of the 19 trials of fluorescein injected at PC6, 15 (79%) were associated with slow diffusion of the dye proximally along a path matching closely with the pericardium meridian. Furthermore, the dye emerged and coalesced proximally at exactly acupoint PC3. Injections of ICG at the acupoints PC5, PC6, or PC7 showed a similar trajectory close to the injection site but diverged when migrating proximally, failing converge on acupoint PC3. Injections of either dye at an adjacent PC6-control did not generate any notable linear pathway. Both ultrasound imaging and vein-locating device did not reveal any corresponding vessels (arterial or venous) at the visualized tracer pathway but did demonstrate correlations with intermuscular fascia.

[Effect of electroacupuncture combined with aerobic exercise on IGF-I /Akt pathway in skeletal muscle of aging rats].

OBJECTIVE: To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein. METHODS: Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot. RESULTS: In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (P<0.05). (2) Compared with YC group, the increase of the expression of IGF-I mRNA in YEA group was more obvious(P=0.051). (3)The expression of p-Akt and p-mTOR in YA group was significantly higher than that in YC group (P<0.05), and the expressionof p-mTOR, p-p70S6K also showed an increasing trend in YEA group (P>0.05). CONCLUSION: Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.

[Effect of acupuncture on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage].

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH. METHODS: Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in brain were detected by the method of Western blot. RESULTS: Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced (P<0.01, P<0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased (P<0.01, P<0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1ß and IL-18 in brain tissue in the model group were increased (P<0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1ß and IL-18 in brain tissue in the acupuncture group were reduced (P<0.01). CONCLUSION: Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1ß and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

[Display of low hydraulic resistance channels along Conception Vessel by in vivo fluorography in rats].

OBJECTIVE: To display the low hydraulic resistance channel along the running course of the Conception Vessel (CV) by using in vivo fluorography, so as to provide evidence for the existence of meridians of traditional Chinese medicine from the aspect of interstitial fluid channel. METHODS: A total of 24 male SD rats were randomly divided into 3 groups, namely CV-low impedance spots (CV-LIS), CV-low hydraulic resistance points (CV-LHRP) and non-meridian points (NMP) groups (n＝8 in each group). The CV-LIS (the imaged line between the xiphoid process and symphysis pubis), CV-LHRP (lateral and parallel to LIS) and NMP (lateral and parallel to CV-LHRP) were detected by using meridian detector and biofluid resistance meter, respectively. Sodium fluorescein solution (1%) was injected into the spot (A-spot, upper 1/5 of the CV-LIS), and one of the NMP (about 1 cm lateral and parallel to the A-spot, and the mid-point between the Kidney and Stomach meridian running courses) by using a microsyringe for observing the migration trace of sodium fluorescein. RESULTS: After injection of fluorescein, the migration trace of fluorescein appeared along the CV-LIS and CV-LHRP lines, and only local diffusion was found in the NMP group. The migration trace lengths along the CV-LIS and CV-LHRP were significantly longer than that of the NMP group (P<0.01), and the migration width of CV-LIS and CV-LHRP groups was significantly smaller than that of the NMP group (P<0.01). The migration speed of CV-LIS and CV-LHRP groups was significantly higher than that of the NMP group (P<0.01). CONCLUSION: Fluorography is able to be used to display the running course of CV, possibly supporting the existence of meridians from the interstitial fluid channel and providing a new method for visualization of meridians.

[Preliminary observation on imbalance degree of impedance in extracellular fluid of cells in the twelve meridians in healthy subjects].

OBJECTIVE: To calculate the imbalance degree (IBD) of left-right meridian (IBD-LRM), IBD of exterior-interior meridian (IBD-EIM) and IBD of hand-foot meridians (IBD-HFM) of impedance in extracellular fluid of cells in twelve meridians of healthy subjects, so as to provide foundation for meridian diagnosis. METHODS: A total of 31 healthy volunteers were enrolled and bioelectrical impedance spectroscopy (BIS) was applied. The constant current (from 1 to 100 kHz, 200 µA) was connected into the bilateral twelve meridians through two excitation electrodes with a distance of 10 cm. Two measuring electrodes, with an interval of 5 cm, were set in between the two excitation electrodes to collect the voltage amplitude and phase. The Cole-Cole curve fitting was used to calculate the impedance of extracellular fluid of cells in the twelve meridians; the IBD-LRM, IBD-EIM and IBD-HFM as well as their absolute values were calculated. RESULTS: The impedance of extracellular fluid in the left side was higher than that in right side in the large intestine meridian, the small intestine meridian and the bladder meridian (P<0.05, P<0.01). The mean value of IBD-LRM of extracellular fluid was (4.0±1.4) %; the mean value of absolute value of IBD-LRM was (15.0±1.1) %; the maximum absolute value of IBD-LRM was the bladder meridian. The mean value of IBD-EIM was (3.3±1.0) %; the mean value of absolute value of IBD-EIM was (17.9±1.6) %; the maximum absolute value of IBD-EIM was the bladder meridian and the kidney meridian. The impedance of extracellular fluid of hand jueyin meridian, hand taiyin meridian and hand shaoyin meridian were lower than those of foot meridians. The mean value of IBD-HFM was (-2.6±1.1) %; the mean value of absolute value of IBD-HFM was (19.7±1.7) %; the maximum absolute value of IBD-HFM was shaoyang meridian; the imbalance of yin meridians was greater than yang meridians. There were significant differences in impedance of extracellular fluid between left and right and between hands and feet (P<0.05, P<0.01). CONCLUSION: The extracellular fluid of left-right meridians of healthy subjects is different, but the absolute value of IBD is low; the mean value of exterior meridian and interior meridian is very close, and the absolute value of IBD is medium; the impedance of the foot meridians are greater than the hand meridians, and the absolute value of IBD is relatively high.

[Exosomes and their roles in diabetes mellitus and its complications: from pathogenic, diagnostic and therapeutical perspectives].

Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.

["Three yin and three yang" subarea division in the body and acupuncture effect].

Under the revised demand of theoretic development in clinical practice and scientific research of acupuncture and moxibustion, the reconstruction of the theory was discussed on the "three yin and three yang" subarea division in the body and acupuncture effect in line with the traditional thinking of Chinese medicine so as to explore the longitudinal foundation and rule in the human body for the "effective stimulation". ①Based on the theory of "qi-space correlation" in Internal Classic and the source of nomenclature of "three yin and three yang", the body is divided in stereo zone in accordance with the theory of "three yin and three yang". ②In view of theoretical reasoning and practical interpretation, it is expounded that the same longitudinal stereo zone subarea in the body could respond to diseases and generate therapeutic effects. ③It is pointed out that the subareas of "three yin and three yang" in the body are closely related to meridians and collaterals, which is the basis of the spatial structure and and physical effect. The importance of the "body" itself is ignored nowadays because of the conventional thinking of "qi and blood" in traditional Chinese medicine.

[Comparison of Extracellular and Intracellular Fluid Distribution Between Stomach Meridian or Gallbladder Meridian and Their Neighboring Tissues of Lower Leg in Healthy Volunteers].

OBJECTIVE: To compare differences of extracellular fluid impedance (Re) and intracellular fluid impedance (Ri) between the Stomach(ST) Meridian or Gallbladder(GB) Meridian and their neighboring non-meridian sites of the left lower leg at the same level, so as to explore the distribution characteristics of body fluid in the meridian. METHODS: Sixteen healthy volunteers were enrolled in the present study. The Re and Ri were detected by using Ag/AgCl electrodes and a digital lock-in amplifier. The measuring electrodes (at an interval of about 3 cm) were separately fixed to the skin sites covering the running courses of the ST Meridian (in the lateral interspace of the anterior tibial muscle)and the GB Meridian (in the interspace of the anterior edge of the fibula), and the excitation electrodes (at an interval of about 9 cm) respectively fixed to the skin sites covering the anterior tibial muscle and the interspace between the anterior tibial muscle and the tibia (about 2 cm and 5 cm lateral to the ST and GB meridians, and about 3－4 cm and 6－8 cm lateral to the ST and GB meridians, respectively). A 100 µA constant current with frequencies from 1 kHz to 100 kHz delivered via an excitation electrode was applied to the site (control spots of the ST Meridian), and signals of the voltage amplitude and phase difference of the tissues fed to the lock-in amplifier via the measuring electrode were collected, followed by measuring those of the GB Meridian and control sites. The circumference of the lower leg around the two excitation and measuring electrodes was measured. Then the cole-cole curve fitting was performed to calculate the Ri and Re, as well as the intracellular fluid resistivity (ρi) and extracellular fluid resistivity (ρe) of the ST and GB meridians, the related muscles and interspace lateral to ST or GB (ST/GB) meridians at the same level. RESULTS: The Ri and Re (Ω) values of the ST, GB, the muscle lateral to ST/GB and the interspace lateral to ST/GB were 19.1±1.3 and 28.3±1.4, 15.8±1.9 and 25.7±2.0, 19.6±1.3 and 31.3±1.6, and 19.4±1.2 and 32.4±1.6, respectively. The Re values were significantly lower at the ST and GB meridians than at the muscle lateral to and the interspace lateral to both meridians (P<0.05). The ρi and ρe values (Ω•cm) of the ST, GB, the muscle lateral to and the interspace lateral to ST/GB were 658.9±78.5 and 953.8±75.3, 528.0±90.1 and 833.9±101.7, 669.9±71.8 and 1 059.8±86.0, 655.9±64.8 and 1 099.3±93.3, respectively. The ρi and ρe values were significantly lower at the GB Meridian Than at the other three locntions, and the ρe value of ST Meridian was significantly lower than those of the muscle lateral to and the interspace lateral to ST/GB meridians (P<0.01)．. CONCLUSION: The Ri, Re, ρi and ρe values of the ST and GB meridians are significantly lower than those of their neighboring tissues at the same levels of the lower leg, suggesting a more extracellular fluid in the meridian running course and providing evidence for our speculation that the meridian is a hydraulic resistance channel.