Exploration of Ideas and Strategies for TCM Modernization Experimental Research Based on Precise Messenger Targeting of Exosomes and TCM Supramolecular "Qi Chromatography" Theory / 中国实验方剂学杂志

Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.

Investigation of Role of TCM Supramolecular "Qi Chromatography" in Modernization of TCM Theory of Epidemic Diseases Caused by SARS-CoV-2 / 中国实验方剂学杂志

In this paper, based on the supramolecular "Qi chromatography" of traditional Chinese medicine (TCM), combined with the characteristics of corona virus disease 2019 (COVID-19), the historical origin and characteristics of theoretical research on the treatment of epidemic diseases by TCM were analyzed retrospectively, and the key scientific problems for achieving its modernization were proposed, and the countermeasures were illustrated. In fact, the emergence and development history of TCM epidemic theory is a comprehensive and scientific understanding of biomolecular chemistry for epidemic caused by pathogen. From the exploration of the cause of abnormal Qi to the epidemic pathogenic factor, from the treatment based on syndrome differentiation by six meridians to by the defensive Qi and nutrient blood and the triple energizer, which is gradually close to the modern theoretical system of infectious diseases and immunology, all of which are stamped with brand of TCM supramolecular "Qi chromatography" theory. In the long history of biological evolution in nature, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as epidemic pathogenic factor in TCM, human body and Chinese materia medica are biological supramolecules at a specific stage of evolution in nature, which are controlled by the "imprinting templates" of molecular society in gradual biomolecules, with the unchanged laws of mutual advancement, mutation, suitability and mutual restriction. Based on the analysis of the law of supramolecular action hiding in the prevention and treatment of epidemic diseases dealt with TCM on procession of principle-method-recipe-medicines, this paper discusses the key scientific problems of its modernization and puts forward the solutions. It can not only clarify the scientific principle of the prevention and treatment with TCM, develop the multi-component Chinese medicine, accelerate the control of the epidemic situation, but also promote the solution of original frontier key scientific problems such as the material basis of meridians, viscera and syndromes, and the compatibility law of the TCM prescription, in order to protect the existing medical resources and open up a new situation in the modernization of TCM research.

Consistency Analysis of “Imprinting Templates” of Chinese Medicine Preparations Based on Dynamic Volatile Components in Houttuyniae Herba / 中国实验方剂学杂志

Objective:The homogeneity regularity of "imprinting templates" of compound preparation of traditional Chinese medicine(TCM) was revealed, which provided the basis for effectively controlling the quality of compound preparation of TCM, by clarifying the dynamic changeability in number and content of volatile ingredients in different batches of Houttuyniae Herba. Method:The volatile oil of Houttuyniae Herba was extracted by steam distillation.The volatile components in 11 batches of Houttuyniae Herba were determined by GC-MS(electron ionization, ion source temperature of 230℃, detection range of m/z 40-500) combined with literature and ChemicalBook database.The relative content of each component was calculated by peak area normalization method and analyzed by the total quantum statistical moments of fingerprint. Result:There were only 15 common ingredients in the volatile oil from 11 batches of Houttuyniae Herba, accounting for 3.35%of total number and 73.94%of total content, while the number of non-common ingredients was 433, accounting for 96.65%of total number.However, the RSD of total quantum first moment of GC-MS fingerprint was 6.8%, the RSD of total quantum second moment was 14.8%(RSD of standard deviation was 7.4%), and the RSD of similarity of total quantum statistical moment was 3.8%.The type and content of volatile ingredients in Houttuyniae Herba were heterogeneous, but their chromatographic behavior of GC-MS fingerprint was uniform, the whole "imprinting templates" was similar. Conclusion:The total quantum statistical moment(similarity) of TCM fingerprint is applicable to quality control of dynamic Chinese medicines, which will play a breakthrough role in the study of homogeneity and stability of material reference and compound preparation for ancient classical formulas.

Application of independently-designed three-demensional printed navigation templates for hepatectomy in hepatic surgical oncology / 中华肝胆外科杂志

Objective@#To investigate the clinical value of independently-designed three-demensional printed navigation templates for hepatectomy in hepatic surgical oncology.@*Methods@#A retrospective study was conducted on 45 patients (including 36 males and 9 females, aged from 40 to 70 years) with hepatocelluar carcinoma treated by hepatoctomy from Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital from June 2016 to June 2018. These patients were divided into observation group (patients conducted with the 3D navigation-template-aided operation, n=25) and control group (patients conducted with regular operation, n=20) according to operation approach. Virtual liver resection volume and actual liver resection volume were calculated in the observation group, and the correlationship between the volume of virtual liver resection and actual liver resection was analyzed by Pearson correlation analysis. The operative time, intraoperative blood loss, intraoperative intrahepatic duct injury and postoperative hospital stay were compared between the two groups.@*Results@#In the observation group, 3D modeling was successfully completed and intrahepatic and extrahepatic duct reconstruction was successful, surgical simulation. There were no statistically significant difference between the virtual and actual resected liver volume in the observation group (P>0.05). The virtual resected liver volume was positively correlated with the actual resected liver volume (r=0.991, P<0.05). Volume of intraoperative blood loss in the observation group was lower than that in the control group [(245.1±22.3) ml vs. (308.6±19.9) ml], and the length of hospital stay was shorter than that in the control group [(7.4±0.2) d vs. (8.6±0.4) d], the difference was statistically significant (P<0.05). There was no accidental injury of intrahepatic duct in the observation group, 1 case of accidental injury of middle hepatic vein and 1 case of accidental injury of secondary branch of right hepatic vein in the control group. The AST of the observation group was significantly reduced compared with that of the control group on the 4 th and 7th days after the operation, and the difference was statistically significant (P<0.05).@*Conclusions@#3D reconstruction of liver based on high quality MR images, can facilitate restoring the adjoint relationship between hepatic duct system and liver tumor. 3D printed navigation templates effectively guide certain kinds of hepatectomy, ensure that the cutting edge at the same time protect the rest of the liver tissue, reduce bleeding and accidental damage, realize accurate tumor resection.

Application of independently-designed three-demensional printed navigation templates for hepatectomy in hepatic surgical oncology / 中华肝胆外科杂志

Objective To investigate the clinical value of independently-designed three-demensional printed navigation templates for hepatectomy in hepatic surgical oncology.Methods A retrospective study was conducted on 45 patients (including 36 males and 9 females,aged from 40 to 70 years) with hepatocelluar carcinoma treated by hepatoctomy from Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital from June 2016 to June 2018.These patients were divided into observation group (patients conducted with the 3D navigation-template-aided operation,n =25) and control group (patients conducted with regular operation,n =20) according to operation approach.Virtual liver resection volume and actual liver resection volume were calculated in the observation group,and the correlationship between the volume of virtual liver resection and actual liver resection was analyzed by Pearson correlation analysis.The operative time,intraoperative blood loss,intraoperative intrahepatic duct injury and postoperative hospital stay were compared between the two groups.Results In the observation group,3D modeling was successfully completed and intrahepatic and extrahepatic duct reconstruction was successful,surgical simulation.There were no statistically significant difference between the virtual and actual resected liver volume in the observation group (P ＞ 0.05).The virtual resected liver volume was positively correlated with the actual resected liver volume (r =0.991,P ＜ 0.05).Volume of intraoperative blood loss in the observation group was lower than that in the control group [(245.1 ±22.3) ml vs.(308.6 ± 19.9) ml],and the length of hospital stay was shorter than that in the control group [(7.4 ±0.2) d vs.(8.6 ±0.4) d],the difference was statistically significant (P ＜ 0.05).There was no accidental injury of intrahepatic duct in the observation group,1 case of accidental injury of middle hepatic vein and 1 case of accidental injury of secondary branch of right hepatic vein in the control group.The AST of the observation group was significantly reduced compared with that of the control group on the 4 th and 7th days after the operation,and the difference was statistically significant (P ＜ 0.05).Conclusions 3D reconstruction of liver based on high quality MR images,can facilitate restoring the adjoint relationship between hepatic duct system and liver tumor.3D printed navigation templates effectively guide certain kinds of hepatectomy,ensure that the cutting edge at the same time protect the rest of the liver tissue,reduce bleeding and accidental damage,realize accurate tumor resection.

A Review of Current Clinical Applications of Three-Dimensional Printing in Spine Surgery

Three-dimensional (3D) printing is a transformative technology with a potentially wide range of applications in the field of orthopaedic spine surgery. This article aims to review the current applications, limitations, and future developments of 3D printing technology in orthopaedic spine surgery. Current preoperative applications of 3D printing include construction of complex 3D anatomic models for improved visual understanding, preoperative surgical planning, and surgical simulations for resident education. Intraoperatively, 3D printers have been successfully used in surgical guidance systems and in the creation of patient specific implantable devices. Furthermore, 3D printing is revolutionizing the field of regenerative medicine and tissue engineering, allowing construction of biocompatible scaffolds suitable for cell growth and vasculature. Advances in printing technology and evidence of positive clinical outcomes are needed before there is an expansion of 3D printing applied to the clinical setting.

A review of screw implantation accuracy in thoracolumbar vertebral pedicle / 临床外科杂志

Pedicle screw fixation is widely applied to spinal surgery owing to its advantages of maitaining the stability of spine,promoting the bone graft fusing and so on. Remarkably implantation accu-racy is not only closely related to ultimate fixation,but also can affect the incidence and the severity of complications. Consequently,to improve screw implantation accuracy is one of the goals that spinal sur-geons always pursue. In recent years,newly-developed techniques have been preliminarily used in clinic. An overview on the progresses of these techniques in China and overseas is presented here.

Recent advances of three-dimensional printing technology in orthopaedics / 天津医药

@#Orthopaedic surgeons mainly use X-ray, CT, and MR imaging data for disease analysis, diagnosis and treatment, which often rely on the experience of doctors and lack of three-dimensional (3D) visual and tactile sense. The 3D printing technology has developed rapidly in recent years, which can quickly convert patient virtual images into threedimensional physical model. It also can build customized personalized structures to fit very specific defects within body. At present, 3D printing technology has been widely used in the diagnosis, treatment and rehabilitation of orthopedic diseases. In addition, the biological printing technology combining materials and cells may be a possible future for achieving regeneration of musculoskeletal tissue. This article aims to review the advanced research of 3D printing technology in orthopaedics, to summarize the existing problems and look forward to the future.

Populational brain models of diffusion tensor imaging for statistical analysis: a complementary information in common space

Abstract Introduction: The search for human brain templates has been progressing in the past decades and in order to understand disease patterns a need for a standard diffusion tensor imaging (DTI) dataset was raised. For this purposes, some DTI templates were developed which assist group analysis studies. In this study, complementary information to the most commonly used DTI template is proposed in order to offer a patient-specific statistical analysis on diffusion-weighted data. Methods 131 normal subjects were used to reconstruct a population-averaged template. After image pre processing, reconstruction and diagonalization, the eigenvalues and eigenvectors were used to reconstruct the quantitative DTI maps, namely fractional anisotropy (FA), mean diffusivity (MD), relative anisotropy (RA), and radial diffusivity (RD). The mean absolute error (MAE) was calculated using a voxel-wise procedure, which informs the global error regarding the mean intensity value for each quantitative map. Results the MAE values presented a low MAE estimate (max(MAE) = 0.112), showing a reasonable error measure between our DTI-USP-131 template and the classical DTI-JHU-81 approach, which also shows a statistical equivalence (p<0.05) with the classical DTI template. Hence, the complementary standard deviation (SD) maps for each quantitative DTI map can be added to the classical DTI-JHU-81 template. Conclusion In this study, variability DTI maps (SD maps) were reconstructed providing the possibility of a voxel-wise statistical analysis in patient-specific approach. Finally, the brain template (DTI-USP-131) described here was made available for research purposes on the web site (http://dx.doi.org/10.17632/br7bhs4h7m.1), being valuable to research and clinical applications.

Documentos utilizados en la gestión de la integración del proyecto de salud / Documents used in the management of health integration project

Con la nueva estrategia trazada por el Ministerio de Salud Pública (MINSAP) para alcanzar la informatización en el sector de la salud, se crea el Sistema de Información para la Salud (SISalud). Este Sistema tiene como objetivo estandarizar la arquitectura e integrar todas las aplicaciones que lo conforman. Siendo el Grupo de Gestión de Integración de Soluciones (GIS), perteneciente a la Empresa Productora de Software para la Técnica Electrónica (SOFTEL), del Ministerio de las Comunicaciones (MINCOM), el encargado de brindar soporte tecnológico para lograr la integración de las aplicaciones para la salud. Para alcanzarla, GIS define el Proceso de Especificación y Verificación para la Gestión de la Integración. Como todo proceso, existen documentos de entrada y salida en sus actividades, definiendo diferentes plantillas que deben ser utilizadas. Este trabajo tiene como objetivo describir cada documento y plantilla que se usa en el proceso, así como su utilización práctica en el mismo, para alcanzar finalmente, que las aplicaciones que sean desplegadas en el entorno de SISalud estén integradas e interactúen entre ellas; cumpliendo con las políticas y estrategias de desarrollo definidas por el MINCOM y el MINSAP(AU)

With the new strategy outlined by the Ministry of Public Health (MINSAP) to achieve the informatization in the health sector, establishing the Information System for Health (SISalud). This system aims to standardize the architecture and integrate all the applications that comprise it. As the Group Management Integration Solutions (GIS), belonging to the company Softel, Ministry of Communications (MINCOM), in charge of providing technological support for the integration of health applications. To achieve this, GIS defines the Specification and Verification Process for Integration Management. As a process, there are input and output documents in their activities, defining different templates to be used. This paper describes each document and template as well as their practical use in the process, to finally reach that applications that are deployed in the environment SISalud are integrated and interact with them, complying with policies and strategies defined MINCOM and the Ministry of Public Health(AU)

A prospective investigation of the epidemiology of in-hospital cardiopulmonary resuscitation using the international Utstein reporting style / 中华急诊医学杂志

Objective To investigate the usefulness of Utstein template to guide the assessment and study of cardiopulmonary resuscitation (CPR) in our medical practice because it has been popularized in many countries since 1991.Methods A prospective observational study using Utstein CPR registry form to evaluate the epidemiological features and outcomes of 511 patients resuscitated in the emergency department.Results Of 511 CPR patients registered,higher cardiac arrest rates were observed in the group of patients aged 40- 70 years. In 511 CPR patients registered,preexisting chronic diseases were common including cardiovascular diseases ( 190,37.2％ ) cerebrovascular diseases (48,9.4％ ) and respiratory diseases (39,7.6％ ).Of them,173 cardiac arrest patients (33.9％) had underlying cardiac causes,such as acute myocardial infarction (AMI) found in 109 (21.3％) patients,and ventricular fibrillation witnessed during first cardiac monitoring in eighty ( 15.7％ ) patients.The restoration of spontaneous circulation (ROSC) rate and survival rate at discharge of in - hospital cardiac arrest (IHCA) patients were 47.0％ and 13.5％respectively,but 16.7％ and 4.7％ respectively in the out - hospital cardiac arrest (OHCA) patients (P ＜0.01,both ). Conclusions This study indicated that the cardiovascular diseases, cerebrovascular diseases,and respiratory diseases were the most common preexisting chronic diseases found in cardiac arrest patients.Myocardial infarct,stroke and trauma were the most common precipitation causes of cardiac arrest in the recruited patients.The rates of ROSC and survival at discharge were significantly higher in statistics in patients with IHCA than those in ones with OHCA.

Diagrama ortodôntico individualizado Trevisi / Trevisi individualized orthodontic arch form diagram

As pesquisas sobre formas de arcos vêm demonstrando, desde o início do século 20, que um dos fatores para manter a estabilidade pós-tratamento ortodôntico é não alterar consideravelmente a forma do arco mandibular do paciente, a distância intercaninos e a distância intermolares. A proposta dessa investigação foi idealizar uma forma de arco ortodôntica ideal ao paciente, observando a forma original, analisando a necessidade ou não de fazer algumas modificações, considerando a forma, o diâmetro anterior e o diâmetro posterior do arco mandibular. A recomendação é manter a forma do arco, caso este não apresente alterações significativas. A metodologia proposta é prática, sobrepondo os templates sobre o modelo de gesso inferior do paciente na região anterior pela vestibular de canino a canino e na região de molares no terço cervical, exatamente no sulco gengival. Uma vez selecionada a forma apropriada do arco ortodôntico ao paciente, confeccionar os arcos de aço sobre o diagrama apropriado que serão utilizados no final do alinhamento, na fase da biomecânica (fechamento de espaços) e na fase de detalhe e acabamento

Research on arch form since the early 20th century has shown that a successful stability after orthodontic treatment can be achieved if the orthodontist refrains from significantly altering the patient’s mandibular arch form, intercanine width and intermolar width. Thus, this research aimed to devise an ideal archwire form for the patient about to undergo orthodontic treatment. An archwire form that could prove ideal for the patient based on his/her original dental arch form, while determining whether or not changes are required in light of the form, anterior diameter and posterior diameter of the mandibular dental arch. The author’s recommendation is that the patient’s original dental arch form be preserved, unless it has undergone significant changes. The proposed methodology is straightforward. It consists in superimposing the templates buccally over the patient’s mandibular cast, from canine to canine, and in the molar region in the cervical third, precisely on the gingival sulcus.Once an arch form suitable to the patient has been found, the orthodontist can then proceed to produce - guided by the appropriate template - the steel archwires that will be used at the end of the alignment phase, in the biomechanics phase (space closure) and in the detailing and finishing phase

A multi- centre study of cardiopulmonary resuscitation by using the Hainan Utstein templates for resuscitation registries / 中华急诊医学杂志

Objective To study the Hainan Utstein templates used for cardiac arrest and resuscitation registries to evaluate the epidemiological characteristics and outcomes of the patients with CPR by multi-center study. Methodsccording to the Utstein templates for cardiac arrest and CPR set by International Liaison Committee on resuscitation in 2004, a Hainan Utstein CPR registry chart was designed and a prospective descriptive study was carried out to evaluate the epidemiological characteristics, impact factors and outcomes of the patients with resuscitation attempt in emergency departments of thirteen hospitals in Hainan Island between January 2007 and December 2010.Results Of 1125 patients with cardiac arrest, male accounted for 73. 8％ and female was 26. 2％. The mean ( ± S. D) age of the cardiac arrest patients was 53.9 ± 13. 1 years old.Coronary heart diseases and hypertension were the most common preexisting chronic diseases in the studied patients. The ROSC rate and discharge rates after survival in 1125 patients with CPR were 23. 8％ and 7.4％ respectively. The ROSC rate and discharge rates after survival were 36. 3％ and 11.6％ in the in-hospital cardiac arrest (IHCA) group, respectively whereas 11.5％ and 3. 3％ in out-hospital cardiac arrest (OHCA) group. Of 188 patients with ventricular fibrillation/Pulseless ventricular tachycardia, the ROSC rate and discharge rate after survival were 58.0％and 21.8％,respectively. Of them, 448 (39. 8％ ) of the cardiac arrest patients had underlying cardiac causes, and the ROSC rate and discharge rate after survival were 36. 3％ and 11.5％ respectively in IHCA group whereas 11.6％ and 3. 3％ in OHCA group. The ROSC rate and discharge rate after survival were 69. 8％ and 7. 4％respectively in the tertiary hospitals whereas 30. 2％ and 7. 3％ in the secondary hospitals. Conclusions Patients experienced cardiac arrest were predominantly male. Coronary heart disease and hypertension were the two most common preexisting chronic diseases. The ROSC rate and discharge rate of patients with IHCA were higher than those with OHCA. ROSC rate and discharge rate after survival were higher in the ventriculat fibrillation/Pulseless ventricular tachycardia group than the other cardiac rhythms first witnessed groups. The time delayed of starting CPR after onset of cardiac arrest had a critical impact on survival and discharge rate in both IHCA and OHCA groups.

Differential templates in foundation of staging by skeletal age on juvenile and children with normal occlusion in Shandong / 中华医学美学美容杂志

Objective To establish the differential templates of juvenile and children in Shandong with normal occlusion, according to the group of skeletal age. Methods 212 juvenile and children at the age of 8-16 years (107 males and 105 females) with normal occlusion in Shandong natives were took cephalomatric radiographs, and divided into different groups by cervical vertebrae skeletal age. Then these cephalomatric radiographs were scanned on the computer and 14 skeletal landmarks were vectorizated. An analytical method of Ricketts and McNamara with WinCept 7.0 was used to make statistics and variance analysis among gender and every group of cervical vertebrae skeletal age,and then established the templates. Results The juvenile and children in Shandong natives with normal occlusion had different templates. Conclusion By overlapping the same skeletal age of templates by SN plane, we can see that male face outline is greater than female and male mandibular plane angle is smaller than female. By overlapping the same gender of templates, there is a developmental trend of mandibular bone to be forward and downward, and to revolve anticlockwise with age.

Detailed Clinical Models: A Review / 대한의료정보학회지

OBJECTIVES: Due to the increasing use of electronic patient records and other health care information technology, we see an increase in requests to utilize these data. A highly level of standardization is required during the gathering of these data in the clinical context in order to use it for analyses. Detailed Clinical Models (DCM) have been created toward this purpose and several initiatives have been implemented in various parts of the world to create standardized models. This paper presents a review of DCM. METHODS: Two types of analyses are presented; one comparing DCM against health care information architectures and a second bottom up approach from concept analysis to representation. In addition core parts of the draft ISO standard 13972 on DCM are used such as clinician involvement, data element specification, modeling, meta information, and repository and governance. RESULTS: Six initiatives were selected: Intermountain Healthcare, 13606/OpenEHR Archetypes, Clinical Templates, Clinical Contents Models, Health Level 7 templates, and Dutch Detailed Clinical Models. Each model selected was reviewed for their overall development, involvement of clinicians, use of data types, code bindings, expressing semantics, modeling, meta information, use of repository and governance. CONCLUSIONS: Using both a top down and bottom up approach to comparison reveals many commonalties and differences between initiatives. Important differences include the use of or lack of a reference model and expressiveness of models. Applying clinical data element standards facilitates the use of conceptual DCM models in different technical representations.

Maxillofacial esthetics by three dimensional facial morphometrics

This study was performed to investigate the average anthropometric value of normal Korean men and women and to compare the preceding literatures. Additionally, average Korean profilogram was made to serve as a template for diagnosis of facial form. Eighty five Korean subjects(41 men, 44 women) aged between 21 to 26 were selected by members of the author's department on the basis of intact dentition and Class I occlusion without facial asymmetry. Frontal and lateral photographs were taken under standardized condition with digital camera. The image was magnified and adjusted according to the FH plane of cephalometric radiographs and digitized using personal computer. To compare the Western beauty, 25 esthetically pleasing female was selected to measure various angle and distance of the face. 1. It was possible to calculate the mean coordinate value of Korean normal samples which enables the direct visualization and comparison with the use of template. The method in this study was easy to applicate under the Microsoft Windows bases. 2. Maxillary vertical hypoplasia, upper and lower lip protrusion was characteristics of Korean norms and relatively narrow alar base distance, less conspicuous nasal projection was observed. As the vermilion exposure and upper lip length was more than western norm, chin looks shorter than western. To compare the Korean and Western esthetically pleasing profile, facial convexity and nose was less conspicuous in Korean women.

Generic physical mechanisms of morphogenesis and pattern formation as determinants in the evolution of multicellular organization.

Early embryos of metazoan species are subject to the same set of physical forces and interactions as any small parcels of semi-solid material, living or nonliving. It is proposed that such "generic" properties of embryonic tissues have played a major role in the evolution of biological form and pattern by providing an array of morphological templates, during the early stages of metazoan phylogeny, upon which natural selection could act. The generic physical mechanisms considered include sedimentation, diffusion, and reaction–diffusion coupling, all of which can give rise to chemical nonuniformities (including periodic patterns) in eggs and small multicellular aggregates, and differential adhesion, which can lead to the formation of boundaries of non-mixing between adjacent cell populations. Generic mechanisms that produce chemical patterns, acting in concern with the capacity of cells to modulate their adhesivity (presumed to be a primitive, defining property of metazoa), could lead to multilayered gastrulae of various types, segmental organization, and many of the other distinguishing characteristics of extant and extinct metazoan body plans. Similar generic mechanisms, acting on small tissue primordia during and subsequent to the establishment of the major body plans, could have given rise to the forms of organs, such as the vertebrate limbs. Generic physical processes acting on a single system of cells and cell products can often produce a widely divergent set of morphological phenotypes, and these are proposed to be the raw material of the evolution of form. The establishment of any ecologically successful form by these mechanisms will be followed, under this hypothesis, by a period of genetic evolution, in which the recruitment of gene products to produce the "generically templated" morphologies by redundant pathways would be favoured by intense selection, leading to extensive genetic change with little impact on the fossil record. In this view, the stabilizing and reinforcing functions of natural selection are more important than its ability to effect incremental change in morphology. Aspects of evolution which are problematic from the standard neo-Darwinian viewpoint, or not considered within that framework, but which follow in a straightforward fashion from the view presented here, include the beginnings of an understanding of why organisms have the structure and appearance they' do, why homoplasy (the recurrent evolution of certain forms) is so prevalent, why evolution has the tempo and mode it does ("punctuated equilibrium"), and why a "rapid" burst of morphological evolution occurred so soon after the origin of the metazoa.