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.

Brain structure underlying the empathizing-systemizing difference in children with autism spectrum disorder.

BACKGROUND: Behavioral research has shown that children with autism spectrum disorder (ASD) have a higher empathizing-systemizing difference (D score) than normal children. However, there is no research about the neuroanatomical mechanisms of the empathizing-systemizing difference in children with ASD. METHODS: Participants comprised 41 children with ASD and 39 typically developing (TD) children aged 6‒12 years. Empathizing-systemizing difference was estimated using the D score from the Chinese version of Children's Empathy Quotient and Systemizing Quotient. We quantified brain morphometry, including global and regional brain volumes and surface-based cortical measures (cortical thickness, surface area, and gyrification) via structural magnetic resonance imaging. RESULTS: We found that the D score was significantly negatively associated with amygdala gray matter volume [ß = -0.16; 95% confidence interval (CI): -0.30, -0.02; P value = 0.030] in children with ASD. There was a significantly negative association between D score and gyrification in the left lateral occipital cortex (LOC) in children with ASD (B = -0.10; SE = 0.03; cluster-wise P value = 0.006) and a significantly positive association between D score and gyrification in the right fusiform in TD children (B = 0.10; SE = 0.03; cluster-wise P value = 0.022). Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume (ß = 0.19; 95% CI 0.04, 0.35; P value = 0.013) and left LOC gyrification (ß = 0.11; 95% CI 0.05, 0.17; P value = 0.001) but not in right fusiform gyrification (ß = 0.08; 95% CI -0.02, 0.17; P value = 0.105). CONCLUSIONS: Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing-systemizing difference in children with ASD but not in TD children. Large-scale neuroimaging studies are necessary to test the replicability of our findings.

A predictive model for identifying secondary underlying diseases of hemophagocytic lymphohistiocytosis.

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH. Methods: We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the ß regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH. Results: The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein-Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P<0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P<0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P<0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932). Conclusion: The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease.

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.

Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value.

Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.

The gut microbiota-bile acid axis: A potential therapeutic target for liver fibrosis.

Liver fibrosis involves the proliferation and deposition of extracellular matrix on liver tissues owing to various etiologies (including viral, alcohol, immune, and metabolic factors), ultimately leading to structural and functional abnormalities in the liver. If not effectively treated, liver fibrosis, a pivotal stage in the path to chronic liver disease, can progress to cirrhosis and eventually liver cancer; unfortunately, no specific clinical treatment for liver fibrosis has been established to date. In liver fibrosis cases, both the gut microbiota and bile acid metabolism are disrupted. As metabolites of the gut microbiota, bile acids have been linked to the progression of liver fibrosis via various pathways, thus implying that the gut microbiota-bile acid axis might play a critical role in the progression of liver fibrosis and could be a target for its reversal. Therefore, in this review, we examined the involvement of the gut microbiota-bile acid axis in liver fibrosis progression to the end of discovering new targets for the prevention, diagnosis, and therapy of chronic liver diseases, including liver fibrosis.

Changes in trabecular bone score and bone mineral density in Chinese HIV-Infected individuals after one year of antiretroviral therapy.

OBJECTIVE: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART. METHODS: We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS. RESULTS: Our study included 233 â€‹PWH (mean age â€‹= â€‹36.6 â€‹± â€‹11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population. CONCLUSIONS: We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.

[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".

hUCB-MSC derived exosomal miR-124 promotes rat liver regeneration after partial hepatectomy via downregulating Foxg1.

Liver regeneration after partial hepatectomy (PH) is a complex and well-orchestrated process involving multiple factors such as cytokines, growth factors, and signaling pathways. MicroRNAs (miRNAs) participate in various biological processes including liver regeneration after PH. In the current study, we investigated the expression and function of human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived exosomal miRNAs on liver regeneration using a rat PH model. We found that hUCB-MSC derived exosomes promoted rat liver regeneration and ameliorated liver injury after PH. MicroRNA microarray was performed to identify the differentially expressed miRNAs in hUCB-MSC derived exosomes involving in liver regeneration after PH. We demonstrated that hUCB-MSC derived exosomal miR-124 could promote liver regeneration and prevent against liver injury after PH in rats. Inhibition of miR-124 abrogated the protective role of hUCB-MSC derived exosome in rat liver regeneration after PH. In addition, we identified that transcription factor Foxg1 was a direct target of miR-124 and miR-124 promoted rat liver cell proliferation via suppressing Foxg1 expression. Furthermore, we demonstrated that hUCB-MSC derived exosomal miR-124 enhanced liver regeneration via inhibiting Foxg1 in rats after PH. In summary, our findings suggest that hUCB-MSC-derived exosomal miR-124 could promote rat liver regeneration after PH via downregulating Foxg1.

Whole blood as an alternative to peripheral blood mononuclear cell for detection of total HIV-1 DNA.

BACKGROUND: A more time saving, convenient, reproducible, and scalable method is needed to assess total HIV-1 DNA levels. METHODS: Frozen whole blood and peripheral blood mononuclear cell (PBMC) samples both 200 µl at the same point were used to detect total HIV-1 DNA. Automatic extraction of total HIV-1 DNA was used to ensure the consistency of sample extraction efficiency. The detection reagent was HIV-1 DNA quantitative detection kit and real-time quantitative PCR was utilized. RESULTS: Of the 44 included patients, 42 were male and 2 were female, with a median age of 33 years. Thirty-three cases were collected after receiving antiviral treatment, with a median duration of treatment of 3 months, and the other 11 cases were collected before antiviral treatment. The median viral load was 1.83 log10 copies/mL, the median CD4 and CD8 count were 94 and 680 cells/µL, and the median CD4/CD8 ratio was 0.18. The results of the two samples were 3.02 ± 0.39 log10 copies/106 PBMCs in PBMC samples and 3.05 ± 0.40 log10 copies/106 PBMCs in whole blood samples. The detection results of the two methods were highly correlated and consistent by using paired t test (P = 0.370), pearson correlation (r = 0.887, P < 0.0001) and intra-group correlation coefficient (ICC = 0.887, P < 0.0001) and bland-altman [4.55% points were outside the 95% limits of agreement (- 0.340 ~ 0.390)]. CONCLUSIONS: The results of the whole blood sample test for total HIV-1 DNA are consistent with those of PBMC samples. In a clinical setting it is recommended to use whole blood samples directly for the evaluation of the HIV reservoir.

Very high baseline HIV viremia impairs efficacy of non-nucleoside reverse transcriptase inhibitor-based ART: a long-term observation in treatment-naïve patients.

BACKGROUND: It is not completely clear whether a very high pre-therapy viral load (≥ 500 000 copies/ml) can impair the virological response. The aim of this study was to examine the influence of very high baseline HIV-RNA levels on long-term virological responses under one type of regimen. METHODS: A retrospective study was performed based on data from two multicenter cohorts in China from January to November 2009, and from May 2013 to December 2015. Untreated HIV infected adults between 18 and 65 years old were recruited before receiving non-nucleoside reverse transcriptase inhibitor-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, good adherence, and were followed for at least 24 weeks. Virological suppression was defined as the first HIV-RNA < 50 copies/ml. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥ 200 copies/ml without virological suppression within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥ 50 copies/ml after virological suppression). Chi-square test, Kaplan-Meier analysis, Cox proportional hazards model and Logistic regression were used to compare virological response between each pretreated viral load stratum. RESULTS: A total of 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. By week 48, rates of virological suppression in three groups (< 100 000, 100 000-500 000 and ≥ 500 000 copies/ml) were 94.1, 85.0, and 63.8%, respectively (P < 0.001). Very high baseline HIV viremia over 500 000 copies/ml were found to be associated with delayed virological suppression (≥ 500 000 vs <  100 000, adjusted relative hazard = 0.455, 95% CI: 0.32-0.65; P < 0.001) as well as incomplete viral suppression (≥ 500 000 vs < 100 000, adjusted odds ratio [aOR] = 6.084, 95% CI: 2.761-13.407; P < 0.001) and viral rebound (≥ 50 000 vs < 100 000, aOR = 3.671, 95% CI: 1.009-13.355, P = 0.048). CONCLUSIONS: Very high levels of pre-treatment HIV-RNA were related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with this clinical character.

[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.

Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters.

BACKGROUND: Among HIV-infected patients initiating antiretroviral therapy (ART), early changes in CD4+ T-cell subsets are well described. However, HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events. Therefore, factors associated with CD4+ T-cell reconstitution need to be determined in this population, which will allow designing effective immunotherapeutic strategies. METHODS: Thirty-one adult patients with baseline CD4+ T-cell count <350 cells/mm3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing, China, from October 2002 to September 2013. Changes in T-cell subsets and associated determinants were measured. RESULTS: Median baseline CD4+ T-cell count was 70 cells/mm3. We found a biphasic reconstitution of T-cell subsets and immune activation: a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years. Baseline CD4+ T-cell count >200 cells/mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs. 27.3% respectively; P = 0.017) and normalized CD4/CD8 ratio. We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907), and 12.4% as cutoff value had a sensitivity of 84.6% and a specificity of 88.2%. CONCLUSIONS: Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy. Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.

Analysis of the Spectral Characteristics of Pure Moxa Stick Burning by Hyperspectral Imaging and Fourier Transform Infrared Spectroscopy.

The objective of this study was to investigate the spectra characteristics (SC) at wavelengths of 400~1000 nm and 2.5~15.5 µm of pure moxa stick (MS) during its 25-minute burning process using new spectral imaging techniques. Spectral images were collected for the burning pure MS at 5, 10, 15, 20, and 25 min using hyperspectral imaging (HSI) and Fourier transform infrared spectroscopy (FTIR) for the first time. The results showed that, at wavelengths of 400~1000 nm, the spectral range of the cross section of MS burning was 750~980 nm; the peak position was 860 nm. At wavelengths of 2.5~15.5 µm, the spectral range of the cross section of MS burning was 3.0~4.0 µm; the peak position was approximately 3.5 µm. The radiation spectra of MS burning include litter red and amount of infrared (but mainly near infrared) wavelengths. The temperature, blood perfusion, and oxygen saturation increase of Shenshu (BL23) after moxibustion radiation were observed too. According to mechanism of photobiological effects and moxibustion biological effects, it was inferred that moxibustion effects should be linked with moxibustion SC. This study provided new data and means for physical properties of moxibustion research.

Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods.

Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy.

Effects of Electroacupuncture Stimulation at "Zusanli" Acupoint on Hepatic NO Release and Blood Perfusion in Mice.

The study is to observe the influence of electroacupuncture (EA) stimulation at "Zusanli" (ST36) on the release of nitric oxide (NO) and blood perfusion (BP) in the liver and further explore whether the hepatic blood perfusion (HBP) changes were regulated by EA ST36 induced NO in nitric oxide synthase inhibited mice. The HBP change of the mice was detected by laser speckle perfusion imaging (LSPI) before and after being given interventions, and the NO in liver tissue was detected by nitric acid reductase in each group. The NO levels and HBP in the L-NAME group were significantly lower than those in the control group (P < 0.01). The NO level and HBP increase in EA group were significantly higher than those in control group (P < 0.05). The NO level in the L-NAME EA group was slightly higher than that in the L-NAME group. The HBP increase in the L-NAME EA group was not statistically significant. These results showed that EA could accelerate the synthesis of NO and thereby increase HBP via vasodilation in liver tissue.

A pilot study on effects of acupuncture and moxibustion by hyperspectral imaging technique.

This study was to observe the effects of acupuncture and moxibustion on spectrum features of acupoint using hyperspectral imaging (HSI) technique. HSI of the Neiguan (PC6) in the acupuncture groups, moxibustion groups, and control groups was scanned by the hyperspectral imager to analyze the spectrum features and the variations within the wavelength of 400-1000 nm and explore the relationship between the spectral characteristics and effects of acupuncture and moxibustion. The light absorption intensity was slightly reduced within the wave band of 540-590 nm after acupuncture. The absorption intensity of PC6 before moxibustion was significantly higher than that after moxibustion, and the maximum reduction was found at the wavelength of 580 nm with 20.5% reduction, P < 0.05. There was no significant change of the spectrum of palm and PC6 and the spectrum curves of the acupoint were basically identical in control group. The light absorption intensity of PC6 of human body was weakened after Acu-mox. Specific wavelengths were all exhibited at 580 nm and the effect of moxibustion was more significant. HSI technique can be used to measure the spectral characteristics of the acupoint areas. This first time research would be significant and beneficial for study on the effect of acupuncture and moxibustion.

Investigation of hepatic blood perfusion by laser speckle imaging and changes of hepatic vasoactive substances in mice after electroacupuncture.

The study was conducted to observe the effect of electroacupuncture (EA) on hepatic blood perfusion (HBP) and vascular regulation. We investigated 60 male anesthetized mice under the following 3 conditions: without EA stimulation (control group); EA stimulation at Zusanli (ST36 group); EA stimulation at nonacupoint (NA group) during 30 min. The HBP was measured using the laser speckle perfusion imaging (LSPI). The level of nitric oxide (NO), endothelin-1 (ET-1), and noradrenaline (NE) in liver tissue was detected by biochemical methods. Results were as follows. At each time point, HBP increase in ST36 group was higher than that in the NA group in anesthetized mice. HBP gradually decreased during 30 min in control group. The level of NO in ST36 group was higher than that in NA group. The level of both ET-1 and NE was the highest in control group, followed by NA group and ST36 group. It is concluded that EA at ST36 could increase HBP possibly by increasing the blood flow velocity (BFV), changing vascular activity, increasing the level of NO, and inhibiting the level of ET-1 in liver tissue.