Application of Biophysical Properties of Meridians in the Visualization of Pericardium Meridian.

Background: The biophysical properties of the meridian system, an important concept of traditional Chinese medicine, include low impedance, resounding voice, and high acoustic conductance, all of which are helpful for elucidating the essence of meridians. Objectives: To visualize the human pericardium meridian (PC) based on the resounding voice property of meridians. Methods: Visualization of the PC was performed by injection of fluorescein sodium at the PC6 acupoint (Neiguan) on the PC. Before injection, percussion active points (PAPs) were identified by the virtue of their resounding voice properties. After injection, the trajectories of fluorescein migration throughout the body surface were recorded and analyzed. The distribution of fluorescein in the tissue was further studied using cross-sections of hind limbs of mini-pigs, in which fluorescein was injected into low impedance points. Results: The identified PAP lines were colocalized with PC. Following intradermal fluorescein injection, 1-3 fluorescent lines, which were unrelated to the arm veins, were observed in 7 of 10 participants; 85.4% of fluorescent signals were coincident with PAPs and their intensity had a negative correlation with the body mass index (r = -0.56, p = 0.045). Cross-sections showed a Y-shaped fluorescence pattern where the two migration lines on the surface were the two vertices of the "Y." Conclusion: The trajectories of fluorescein in the body are suggestive of the anatomical structure of meridians. The PC is related to the deep horizontal interstitial channels that connect to the body surface through vertical interstitial spaces. These biophysical properties and techniques for meridian visualization are valuable for revealing the anatomical structure of meridians.

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.

[Specification and solution of the normative elements in the development of the national standard: "Pure moxa stick"].

This paper introduced the research ideas and methods for the development of the national standard, "Pure moxa stick". According to the orientation of product standard and related documents, on the basis of extensive investigation and in consultation with manufacturers and experts, the problems encountered in this standard development were solved. The general technical requirements were specified in association with the basic experimental data. The technical requirements should not only conform to the current technological status of moxa sticks production, but also present a certain of innovation. The innovation of this standard lies in the concepts of the ratio of leaves to floss, the ratio of whole plant to floss, density, etc. Besides, the main technical requirements of "Pure moxa stick" have been specified, i.e. material, shape and structure, combustion characteristics, physical and chemical characteristics. The development of national standard "Pure moxa stick" contributes to the favorable exploration and practice of the standardization of traditional Chinese medicine and provides the effective reference for the further stan-dardization of acupuncture and moxibustion.

Pilot Study of Blood Perfusion Changes at PC4 and Its Surrounding Points Induced by Acupuncture and Moxibustion.

Acupuncture and moxibustion are widely used in clinical practice; however, the differences between their mechanisms are unclear. In the present study, the response of blood perfusion resulting from acupuncture or moxibustion at Ximen (PC4) and its surrounding points was explored. Using the wavelet method, the differences in the frequency interval of blood flux were observed. Furthermore, the correlations between these points were analyzed. The results suggested that moxibustion could significantly improve blood flow perfusion at PC4 compared to acupuncture; however, there was no significant difference around PC4. The response of blood flux at PC4 to different stimulations was related to the frequency V (0.4-1.6 Hz) component. However, a difference in response at other points was not observed. Correlation analysis showed that both acupuncture and moxibustion could cause a decline in the correlation of blood flux signals at these recorded points, but there was no significant difference between these techniques. The results suggested that, at least in the forearm, the acupuncture or moxibustion only influenced the level of blood perfusion locally.

Differential Proteomics Analysis of the Subcutaneous Connective Tissues in Alcian Blue Tracks along Conception Vessel and Adjacent Nonmeridian in Rats.

In more than half a century, exploring the biological connotation of the meridians was one of the core components of scientific research studies in traditional Chinese medicine (TCM). Based on the previous works of low hydraulic resistance channel (LHRC) along meridians (LHRCM), the differential proteomics between the Alcian blue track (ABT) on LHRC along the conception vessel (CV) and nonmeridians tissue next to the CV were investigated in this study to explore the material basis and biological function of LHRCM. Proteomics based on LC-MS was introduced into the subcutaneous connective tissues (SCT) of ABT along the CV and the adjacent nonmeridian (1 cm from the CV). A total of 2328 proteins were identified from ABT along the CV and adjacent nonmeridian based on data-dependent acquisition (DDA) mode. In total, 1970 proteins were quantified based on the SWATH (sequential window acquisition of all theoretical fragment ions) label-free model, and the nonstandard and quantitative methods of MSALL were applied to analyze the data. There were 468 proteins differentially expressed. GO analytic results showed that the differential proteins were of varieties in molecular function and biological process. Most of differential proteins were involved in metabolic process, cellular process, response to hormone, and response to wounding. Further analysis showed that the upregulated differential proteins involved in ATP metabolism (ATP5E, GAPDH), redox reactions (Gpx-3), and Ca2+ transmembrane transport (CACNA2D1) were closely related to meridian phenomenon and acupuncture effect. These differential proteins would be potential characteristic proteins of the LHRC along the CV in rats which may be useful to deepen the knowledge on LHRCM.

[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.

Changes of Blood Flux at BL21 and Points along BL Meridian Resulted from Acupuncture or Moxibustion: Case Cross Design Study.

Acupuncture (Acup) and moxibustion (Moxi) are commonly used interventions in clinical practice. However, the difference between Acup and moxibustion mechanisms is unclear. In current study, blood perfusion responses resulted from Acup or Moxi at Weishu acupoint (BL21) and control points were explored, respectively. The time series of blood flux signals at BL21 and control points were transformed with Morlet wavelet, and the differences in each frequency interval were observed. The results suggested that acupoint response to different stimulation is a comprehensive process which related to all components of blood perfusion signals. Whereas the different response at control points was not observed, there has been significant difference coherence value between Acup and Moxi stimulation. The results suggested the influence of Acup and Moxi not only on the level of blood perfusion at local area; the intrinsic relevance after stimulation which can be evaluated by coherence analysis is also an appropriate index to distinguish different stimulations.

Response of Blood Perfusion at ST 36 Acupoint after Drinking Cold Glucose or Saline Injection.

Skin blood flux (SkBF) changes caused by drinking cold water are generally associated with vagal tone and osmotic factors in digestive system. According to acupuncture theory, change of SkBF at ST 36 might reflect the functional changes of digestive system. The aim of this study is to analyze the changes of SkBF after drinking 3°C 0.9% saline or 5% glucose injection by monitor blood flux at bilateral ST 36. The results indicated that, after drinking different cold water, the change ratio of SkBF at right side ST 36 has been different. Because all solutions have the same temperature (3°C) and both saline and glucose solution have the same osmolality, suggesting that the SkBF changes resulting from drinking cold water are not regulated just by the vagal tone and osmolality, there must have been other factors. These results have not been consistent with the frequency domain results of heart rate variability (HRV) analysis. Coherence analysis of blood flux signals at bilateral ST 36 indicated that there have been different coherence-frequency curves among different groups in special frequency bands, which suggested that coherence analysis might provide a potential tool to evaluate different status.

Is There Volume Transmission Along Extracellular Fluid Pathways Corresponding to the Acupuncture Meridians?

Volume transmission is a new major communication signaling via extracellular fluid (interstitial fluid) pathways. It was proposed by the current authors that such pathways can explain the meridian phenomena and acupuncture effects. To investigate whether meridian-like structures exist in fish body and operate via volume transmission in extracellular fluid pathways, we injected alcian blue (AB) under anesthesia into Gephyrocharax melanocheir, which has a translucent body. The migration of AB could be seen directly and was recorded by a digital camera. The fish was then embedded and cut transversely to observe the position of tracks in three dimensions. Eight longitudinal threadlike blue tracks were recognized on the fish. The positions of these threadlike tracks were similar to meridians on the human body. Transverse sections showed that these tracks distributed to different layers of distinct subcutaneous loose connective tissues and intermuscular septa. Lymphatic vessels were sometimes associated with the extracellular blue tracks where the migration of AB occurred. Extracellular fluid pathways were found on fish through their transport of AB. These pathways operating via volume transmission appeared to be similar in positions and functions to the acupuncture meridians in Chinese medicine.

[Effect of Needle Embedded in Neiguan (PC6) on Changes of ECG in Chronic Myocardial Ischemia Model Mini-pigs].

Objective To observe the effect of needle embedded in Neiguan (PC6) on electro- cardiogram (ECG) changes in model mini-pigs with chronic myocardial ischemia. Methods The protein shrink narrow ring (Ameroid Ring) was placed in the proximal part of the left coronary anterior descend- ing branch of 12 Chinese mini-pigs to prepare animal model. One died during the modeling. Chronic myo- cardial ischemia mini-pig models were established after 4 weeks. Successfully modeled 11 mini-pigs were divided into the test group (n =6) and the control group (n =5). Needle were embedded in Neiguan (PC6) of the test group and Zusanli (ST36) of the control group at week 4 after modeling. Electroacupuncture (EA) at corresponding acupoint twice (once before embedding and at week 2 after embedding) , 20 min each time. Changes of Q wave of ECG, heart rate, and ST-T interval were observed in the two groups be- fore and after modeling, before and after EA. Results Compared with before modeling in the same group, the absolute value of Q wave both increased in the two groups after modeling (P <0. 05, P <0. 01J. No statistical difference existed in heart rate in the two groups between before and after modeling (P> 0. 05). Compared with before needling in the same group, ST-T interval was prolonged in the test group (P <0. 05). Compared with the control group at the same time point, the absolute value of Q wave was re- duced before EA, ST-T interval was prolonged after EA in the test group (P <0. 05). No statistical differ- ence existed in heart rate between the control group and the test group before EA (P >0. 05). Conclusion Needle embedded in Neiguan (PC6) could arrive at therapeutic effect of myocardial ischemia possibly through improving myocardial blood supply.

[Color spectrum of cupping mark detected by hyperspectral camera:a preliminary observation].

OBJECTIVE: To perform quantitative observation on the color change of local skin after cupping, so as to explore objective and quantitative methods for skin response of cupping. METHODS: Seven health subjects were included. By quantitative meridian cupping instrument, cupping methods with four types of pressures were respectively performed on subjects for 5 min.The spectrum of cupping mark before and after the cupping was collected by hyperspectral camera, and the color change was recorded by digital camera. RESULTS: Before the cupping, the differences of back skin areas were not significant (P>0.05), and its average spectrum indicated two peaks at 540-550 nm and 580-590 nm. After cupping with different pressures, spectrum changes of skin were observed. For -0.02 MPa, the most significant reduction was observed at 550 nm (-12.1%, P<0.05); for -0.03 MPa, the most significant reduction was observed at 540 nm (-22.1%, P<0.05); for -0.04 MPa, the most significant reduction was observed at 610 nm (-26.7%, P<0.05); for -0.05 MPa, the most significant reduction was observed at several spectrums (all P<0.05). CONCLUSIONS: After cupping with different negative pressures, significant changes of spectrum are observed on skin; for different pressures, the spectrums of the most significant changes are different; the hyperspectral camera could be applied to perform quantitative observation on the color change of local skin.

Acupuncture regulates the heart rate variability.

Acupuncture is widely used in clinical practice. According to traditional acupuncture theory, the Neiguan acupoint (PC6) is one of the most commonly used acupoints and is indicated for treating cardiovascular-related disorders. We present the case of a 27-year-old female who had been diagnosed with ventricular septal defect and had undergone surgery to repair the defect at the age of 11 years. The patient had no obvious symptoms, such as palpitations and difficulty breathing. However, while performing electrocardiography (ECG), we found that she suffered from arrhythmia, and therefore, we treated her by acupuncture at the left PC6. An ECG monitor was used to record data during the entire acupuncture procedure, which was divided into the following three segments: prior to, during, and after acupuncture. Various indices of heart rate variability (HRV) were then determined and analyzed. The results indicate that acupuncture can regulate the HRV effectively; however, more studies are needed to confirm this finding.

Finding Blue Tracks in Gephyrocharax melanocheir Fish Similar to the Locations of Acupuncture Meridians after Injecting Alcian Blue.

This study investigated whether a meridian-like distribution of Alcian blue (AB) existed after it was injected into a fish's body and suggested a new animal model for meridian study. Twenty Gephyrocharax melanocheir fish with translucent bodies were injected with AB at a point near the spinal column or the dorsal fin. Distribution of AB was observed using a digital camera and a stereomicroscope. Three or more obvious blue tracks were found: one along the spinal column, another along the posterior margin of the abdomen extending to the superior margin of the anal fin, and a third along both sides of the dorsal fin. They were similar to the locations of the governor, conceptual vessel, and urinary bladder meridians, respectively, on the human body according to the classic theory of traditional Chinese medicine. A few other blue tracks were also found, which apparently did not correspond to any known meridians. The results show that the tracks of AB share important similarities with the locations of classically described meridians and that they are mainly distributed in the interstitial space around bones and blood vessels and inside muscular interstices. This study may provide a new experimental animal model for exploring acupuncture meridians.

[Low back pain of cold-damp pattern treated with electric-thermal Bian-stone therapy and traditional moxibustion: a randomized controlled trial].

OBJECTIVE: To compare the difference in the efficacy on low back pain of cold-damp pattern between electric-thermal Bian-stone therapy and moxibustion box therapy. METHODS: Forty-one cases of low back pain of cold-damp pattern were randomized into an electric-thermal Bian-stone therapy group (group A, 26 cases) and a box moxibustion therapy group (group B, 15 cases). In the group A, the electric-thermal Bian-stone was placed over Shenshu (BL 23) and Weizhong (BL 40). The temperature of stone was adjusted in accordance with patient's comfort. In the group B, moxibustion box was used over Shenshu (BL 23) and Weizhong (BL 40). The treatment was given once every day or every two days. Ten treatments made one session. The symptom and physical signs score of low back pain and the score of cold-damp syndrome were observed before and after treatment in the patients. RESULTS: The symptom and physical signs score of low back pain and the score of cold-damp syndrome were all improved in the two groups (all P < 0.01). The changing rate of symptom and physical signs and syndrome were (37.04 +/- 32.68)% and (22.85 +/- 29.95)% in the group A, and were (47.29 +/- 22.08)% and (23.89 +/- 22.53)% in the group B, respectively, without significant difference in comparison between the two groups (all P > 0.05). CONCLUSION: The efficacy on low back pain of cold-damp pattern treated with the electric-thermal Bian-stone therapy is similar to that of moxibustion box therapy. This therapy is characterized as more convenient, safer operation and less pollution.

[Discussion on the model organism in acupuncture and meridians researches].

Using model organism to replace human subjects for experimental objects is an important part in basic research on acupuncture therapy. In the process of experimental research, the first thing is that if the animal model is suitable for revealing the underlying mechanism of acupuncture intervention, if it is relatively close to structures of the human body. In addition, some factors such as being easy to feed, larger in the volume and body-surface, lesser in fur, stable in the germline and reasonable in the cost should be considered. In current acupuncture study, most experiments were carried out in mice and rats, some were conducted in rabbits and cats, fewer conducted in larger animals like mini-pigs and monkeys. Due to being smaller in both body size and superficial area in the mouse and rat, soft and comate skin in the rabbit and cat, difficult breeding for cattle and horse, experimental studies of acupuncture-meridians are in fact not ideal in these animals. Mini-pig has a larger body size and body surface, being similar to the human body in the skin structure and easy to breed, and the monkey is mostly close to the human in the gene and body size, and is thus an ideal model organism for acupuncture research. Because acupoint and meridians have their space specificity, the usage of larger animal as the model organism is necessary.

Acupoint Activation: Response in Microcirculation and the Role of Mast Cells.

BACKGROUND: According to Traditional Chinese Medicine (TCM) theory, acupuncture effects are based on the integrity function of meridians. Meridians are thought to regulate body function through the normal flow of qi and/or blood. Disturbances in this flow are thought to cause disease, and acupuncture techniques are believed to cure disease by regulating this flow. However, it is still difficult to understand the exact meaning of qi and to evaluate the activation of meridians. Thus, more and more attention has been focused on the relationship of acupuncture and circulation. METHODS: In this narrative review, the authors focus on the state of the art in acupoint activation, microcirculation response, and on investigation of mast cells, based on current literature research. RESULTS: Altogether, 52 references are cited and discussed critically. A schematic diagram of the relationship between acupuncture stimulation, changes of microcirculation and mast cells is presented as result. CONCLUSION: The block diagram presented in this review article shows that mast cells might play an important role in circulation response after acupoint stimulation.

Pilot study of acupuncture point laterality: evidence from heart rate variability.

The specificity of acupuncture points (acupoints) is one of the key concepts in traditional acupuncture theory, but the question of whether there is adequate scientific evidence to prove or disprove specificity has been vigorously debated in recent years. Laterality, or the tendency for acupoints on the right or left side of the body to produce different physiological effects, is an important aspect of acupoint specificity. Data is particularly scarce regarding the laterality of the same channel, same-named acupoint located on opposite sides of the body. The aim of this study was to investigate whether Neiguan (PC6) has laterality. A total of eighteen healthy female volunteers were recruited for this study. Electrocardiograms were recorded and heart rate variability was analyzed before, during, and after PC6 was stimulated on either the left or the right side. The results show that during acupuncture, there were significant differences in the standard deviation of RR intervals (STDRR), root mean square of successive differences between RR intervals (RMSSD), and total power between the left PC6 stimulation group and the right PC6 stimulation group, which indicates that PC6 may have laterality.

Pilot study of blood perfusion coherence along the meridian in forearm.

BACKGROUND: Many studies have explored the relationship between skin microcirculation and meridian activation. However, few studies have examined blood perfusion coherence along the meridians, and other studies have suggested that the skin vasodilator response relates to age. This study investigated blood perfusion coherence characteristics along the meridian of the forearm in healthy volunteers. METHODS: A total of 15 young subjects (25.53 ± 2.20) and 15 middle-aged subjects (50.07 ± 3.37) were recruited for this study. Before experiments, each subject was placed in a temperature-controlled room for 60 min. Skin blood perfusion from five points was recorded simultaneously using a full-field laser perfusion imager before and after inflatable occlusion. The five points comprised three points located on the pericardium meridian, and two points from different locations. Coherence analysis between these points was performed at different frequency intervals from 0.0095 to 2 Hz. RESULTS: In young subjects, the coherence value was unchanged before and after occlusion, and there was no significant difference in coherence value between meridian-meridian points (M-M) and meridian-parameridian points (M-P). In middle-aged subjects, the coherence value increased significantly in both M-M and M-P at frequency intervals of 0.14-0.4 Hz, 0.4-1.6 Hz, and 1.6-2 Hz. However, there was no significant difference in coherence values between M-M and M-P. CONCLUSIONS: Inflatable occlusion can increase middle-aged subjects' blood perfusion coherence value of the forearm. However, there is no specificity in meridian location.

Induction of Hyperalgesia in Pigs through Blocking Low Hydraulic Resistance Channels and Reduction of the Resistance through Acupuncture: A Mechanism of Action of Acupuncture.

According to the classic theory of Chinese medicine, pain is due to the blockage in meridian channels, and acupuncture was invented to treat pain by "dredging" the channels. To test the theory, a hyperalgesia model was made by injecting hydrogel into low hydraulic resistance channel (LHRC) in 12 anaesthetized minipigs. Tail-flick threshold and ear-flick threshold were measured using a thermal radiation dolorimeter, and relative flick threshold (RFT) was calculated. Hydraulic resistance (HR) was measured with a biological HR measuring instrument on low HR points on LHRC and on control points with higher HR located outside LHRC; readings were recorded before, during, and after acupuncture treatment. RFT decreased after blocking the LRHC and was still significantly decreased 2 days and 4 days afterwards. No significant changes occurred when injecting saline into the same points or injecting gel into points outside the channel. Subsequent acupuncture reduced HR on LRHC along meridians but had no significant effect on sites with higher HR located outside LHRC. One of the mechanisms of action of acupuncture treatment for chronic pain may be that acupuncture affects peripheral tissue by reducing the HR in LHRC along meridians, improving the flow of interstitial fluid and removing algogenic substances and thereby relieving pain.

Pathological Changes in Internal Organs after Blocking Low Hydraulic Resistance Channels along the Stomach Meridian in Pigs.

Objective. The correlation between meridians and organs (Zang-fu) is an important aspect of meridian theory. The objective of this paper is to investigate the pathological changes in the organs resulting from blocking low hydraulic resistance channel (LHRC) along the stomach meridian by injecting gel in pigs so as to offer some insight into the correlation between meridians and internal organs. Methods. Four white piglets and twelve black minipigs were divided into four batches and were observed in different periods. Each batch included two pairs of pigs and each pair matched two pigs with similar conditions among which gel was injected into 6~8 low hydraulic resistance points along the the stomach meridian in the experimental pig and the same amount of saline was injected into the same points in the control pig. The state of stomach and intestine was observed 6~10 weeks after the blocking model was developed. Results. The results showed that there were bloated stomach or/and intestine in all the experimental pigs while there were normal states in seven control pigs except one dead during the experiment. Conclusion. The findings confirmed that the blockage of LHRC along the stomach meridian can influence the state of stomach and intestine, leading to a distension on stomach or/and intestine.