Even though there is available literature recommending community engagement in health research, there are still knowledge gaps in how communities might be best engaged in Sub-Saharan Africa. We, therefore, synthesized the existing literature on the current practices, barriers and facilitators, ethical considerations, and gender mainstreaming in the engagement of communities in research in sub-Saharan Africa.this synthesis was developed following the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA). A combination of keywords and medical subject headings was used to search MEDLINE, EMBASE, Global Health Library through OVID SP, the Cochrane Library, PsychINFO, CINAHL, WHO Afro Library, WHO Global Index Medicus and the National Institute for Health Research, for all literature published between 1 January 2000 to 31 July 2021.thirty articles met our inclusion criteria. The key reported facilitators of effective community engagement in research included appropriate community entry and engagement of stakeholders. Barriers to effective community engagement in research included the availability of prohibitive cultural, historical and religious practices; geographical/spatial limitations, difficulties in planning and executing community engagement activities and communication barriers. Awareness creation and sensitization on the research through drama, social media, documentaries, and community durbars are some of the existing practices adopted in engaging communities in research. Gender mainstreaming was not considered appropriately in the engagement of communities in research, as only a few studies made provisions for gender considerations, and most of the time, interchanging gender for sex. Respect for autonomy, privacy and informed consent were the main ethical issues reported.gender mainstreaming and ethical standards were reported as important, but not explored in depth. Gender as a social construct needs to be carefully integrated in the entire research cycle. Clear ethical concerns within a research project have to be co-discussed by the research team, community members and potential research participants. Community engagement (CE) in research can be defined as a process of inclusive participation that supports mutual respect of values, strategies and actions for the authentic partnership of people affiliated with or self-identified by geographic proximity, special interest, or similar situations to address issues affecting the well-being of the community of focus . MeaningEthical CE entails upholding high ethical standards. When we engage the community, we make certain that marginalized or disempowered subgroups in the community are included in the research project . This haDifferent organizations and research bodies use diverse strategies and protocols to engage communities in research activities. However, there is little information on the role gender plays in effective CE, thus justifying the need to assess gender dynamics across the entire spectrum of the research process in African communities . Gender-The rise of community-based participatory research (CBPR) suggests that researchers are becoming more embedded in the communities they are studying and are committed to preventing harm and promoting social justice while conducting research, as well as developing caring relationships. Thus, an awareness of the potential complexities and conflicts and a willingness and ability amongst research collaborators to reflect on such ethical issues throughout the planning and conduct of CBPR are fundamental ,11. CultDespite the available literature recommending CE in health research ,5, thereAnnex 1) are attached as supplementary files. The articles included had to meet the inclusion criteria, and were both from peer-reviewed articles and grey literature. The inclusion criteria were: articles published between 2000 and 2021, contained research on CE or their implementation involving engaging communities. We were specifically interested in issues around gender, ethics, and best practices when engaging communities in research. We included articles published in the English and French languages.To select the studies, we used a combination of keywords and medical subject headings such as “Community Engagement” or “Community Involvement” were used to search 09 databases for all literature published between 1 January 2000 to 31 July 2021. We searched the following databases: MEDLINE, EMBASE, Global Health Library through OVID SP, the Cochrane Library, PsychINFO, CINAHL, WHO Afro Library, WHO Global Index Medicus and the National Institute for Health Research. Commentaries, personal views, and letters to editors were, however, excluded. Citations retrieved from database searches were exported into EndNote X9 to remove duplicate citations and imported into Rayyan QCRI for screening. The protocol for this systematic review was developed following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) . A PRISMTwo authors (LEB and CA) independently screened citations retrieved from database searches based on title and abstract. The titles and the abstracts were screened by applying the previously stated eligibility criteria before assessing the full texts of selected articles for final inclusion in the review. Disagreements between review authors during the screening stage were resolved through discussions and consensus. In the case of non-resolution, a third reviewer was to serve as a tiebreaker. However, this option was not utilized as such disagreement did not occur. The articles were read extensively, and a thematic analysis was carried out. The major codes and themes were summarized in an Excel file. The six-step thematic approach proposed by Braun and Clarke  guided tQuality of evidence:Annex 2 presents the methodological quality assessment of the 30 papers [0 papers ,15,18-450 papers , qualita0 papers  and mixe0 papers ,49 studiDisclaimer: the lead author (guarantor of the manuscript) certifies that the manuscript is an honest, transparent, and accurate account of the research being reported; that no important aspects (objectives) of the study have been omitted; and that any deviations from the study as planned  have been explained.A total of 1383 articles were identified from searching the various databases. The titles and abstracts of these 1383 were reviewed and 89 were retained to be within our scope. A full-text review of the 89 articles was conducted and 30 of them met our inclusion criteria. Annex 3 and Annex 4. Annex 3 presents studies included that were conducted in single site (country) while the Annex 4 presents studies included that were conducted in multiple sites. Regarding the single-country studies, twenty-one studies were identified. Three of the studies were conducted in Zambia, two in Ghana and Nigeria respectively, six studies were conducted in South Africa, four in Malawi and one in Swaziland, Eswatini, Kenyan and Zimbabwe respectively. The studies were conducted between 2003 and 2020. Nineteen of the studies were qualitative designed studies while two were systematic review studies. Also, regarding the multiple country studies, nine studies were identified and these studies were conducted between 2010 and 2018. All of these studies were qualitative approach studies using in-depth interviews or focus groups discussions. The studies were carried out in Botswana, Cameroon, Ethiopia, Ghana, Kenya, Mali, Nigeria, South Africa, Uganda and Zimbabwe; Burkina Faso, Mali and Tanzania; Thailand, India, South Africa and Canada; Zambia and South Africa; South Africa and Zimbabwe; Botswana, South Africa, and Zimbabwe.The characteristics of studies included in the final analysis are listed in Annex 5 presents the themes and sub-themes realized from our qualitative synthesis. Ten out of the 30 studies included in our review reported on current practices in involving communities in research. Two main themes came up based on current practices. They were: awareness creation and sensitization on research co-creation. Fifteen studies also reported on barriers to effective community engagement in research. The barriers reported were prohibitive cultural, historical and religious context, geographical/spatial limitation, ineffective stakeholder engagement, difficulty in planning and executing community engagement activities, community expectations, communication barriers, inadequate representativeness of community stakeholders, logistical challenges, inadequate priorities and negative experience from previous studies. Twenty-two studies reviewed reported on facilitators of effective community engagement in research. The themes reported were: effective community entry and engagement of stakeholders at beginning of the research, effective community engagement strategies, community empowerment, and community motivation. Twelve studies also reported on ethical considerations in engaging communities in research. The themes reported included: cultural considerations, community autonomy, review of research protocols, informed consent, avoidance of community exploitation, ensuring fidelity, risk and benefit, and privacy and confidentiality. Four studies reported on current trends in how gender is taken into account when engaging communities in research. The themes of interest were gender and consent, gender of field workers, and gender equality.Regarding awareness creation as a current practice of community engagement in research, seven sub-themes were reported. They entail the use of drama, use of social media, use of documentaries and digital storytelling, use of open community forums, use of community durbars, use of mobile vans with key messages, and use of leaflets. The proliferation of social media platforms has resulted in much easier and faster information dissemination. They are also effective at influencing people's opinions. As a result, researchers use its effectiveness to disseminate research information. Three of the studies ,30,44 reCommunity capacity building under the theme of co-creation was noted by 4 of the studies as the current practice of community engagement ,22,29,31Concerning the prohibitive cultural, historical and religious context, three sub-themes were reported from seven of the publications included in the review ,37,43,44Two sub-themes emerged in terms of ineffective stakeholder engagement ,39,40. TConcerning communication barriers, seven sub-themes were reported ,40,43,45Three sub-themes entailing failure of previous research to achieve their intended objective, personal questions that communities are not comfortable with from previous research experience, feeling disappointed not being included in the research , feeling of researchers not meeting the expectations of the community ,41.Concerning inadequate priorities, two sub-themes were realized. These comprise competing programs and conflicting agendas. Two studies also argued in their respective studies that when there are multiple research projects running concurrently in communities by different research teams, communities tend to attach different priorities to the various studies which can hinder their willingness and actual involvement in some of the studies.Annex 5. The theme had six sub-themes which comprise engaging first, traditional and religious leaders, engagement of community-level political leaders, engagement of communities during protocol formulation stages, engagement of civil society organizations, social mapping, and paying close attention to clear channels of authority in the local communities.Effective community entry and engagement of stakeholders at beginning of the research was reported by nine of the studies included in our review -41,43,45Engaging the major traditional and religious authorities were considered key, and should be done from the very start of the research cycle ,39-41,43Effective community engagement could be facilitated by ensuring community mobilization through targeted sensitization campaigns to ensure that community members understand the research objectives and deliverables. The utilization of strong communication skills through the adoption of social marketing strategies and the use of new technologies including computers also help to facilitate community engagement in research ,41,43. WRegarding cultural considerations, three sub-themes emerged from our synthesis. These include gaining understanding of community perspectives, beliefs, cultural values, and practices, as well as adopting culturally appropriate ways to communicate research information to communities. The theme also includes the fact that studies involving difficult and complex topics need to be evaluated for their effectiveness in the cultural context within which such studies are being conducted. Regarding the adoption of culturally appropriate ways to communicate research information to communities, for instance, three of the studies argued that there should always be respectful of local community concerns and norms during their engagement for the conduct of research.Concerning community autonomy as an ethical consideration during community engagement, five sub-themes were realized. These comprise the need for the autonomy of communities in decision making to be enhanced, Community Advisory Boards (CAB) being able to carry out their functions independently of the research team in order to protect the community from any unethical research practices, avoidance of structural coercion, avoidance of the use of coercive methods in referral or recruitment of participants, and a need for research involving young people to be evaluated for their effectiveness. Respect the “autonomy” (identity)of communities during decision-making regarding the engagement of the communities in research. This is because, in communities where the majority of people are poor and access to healthcare is limited, researchers sometimes easily persuade community members to participate in research projects by promising free healthcare which ensures that participants do not question the research processes or objections. Another study indicated that Community Advisory Boards (CAB) which are normally formed to serve as watch dogs over the communities, should be able to carry out their functions as gate keepers of the community in independently protecting the communities from unethical research practices.Concerning the informed consent, two sub-themes were reported. These entail a need to obtain community-informed consent before engagement and ensuring appropriate consenting processes in populations with low literacy or limited exposure and experience with research. The need for research institutions to obtain informed consent from communities before engagement in research was considered as a core consideration. Exploitation was one of the main themes realized under ethical practices in engaging communities in research. Two sub-themes were realized from this theme. These entail exploitations of locally recruited researchers through unfair employment practices and power imbalance and dynamics between researchers and communities. Power imbalance and dynamics between researchers and poorer communities could lead to undue inducements which influence communities to participate in studies without fully understanding the risks and benefits, as they are attracted to monetary incentives and healthcare that the projects may come with.Regarding risk and benefit as an ethical practice during community engagement, two sub-themes emerged. These were providing adequate information on research goals, risks, and benefits and avoiding research-related harm to the communities. With regard to providing adequate information on research objectives, risks, and benefits to the communities before engagement, benefits and compensations that come with the research project participation need to be made clear to communities before their engagement. Research-related harm needs to be avoided by researchers when engaging communities in research projects as this is usually the situation. The authors stressed that researchers and research institutions should ensure safety of communities when conducting study activities in communities.According to two of the studies ,44 whichThis systematic review explored current practices, the barriers and facilitators, ethical considerations, and gender mainstreaming in engaging communities in research. A total of 30 publications were reviewed to generate qualitative themes and sub-themes. Two arose based on current practices in involving communities in research. They are awareness creation on the research and co-creation. Prohibitive cultural, historical and religious context, geographical/spatial limitation, ineffective stakeholder engagement, difficulty in planning and executing community engagement activities, community expectations, communication barriers, inadequate representativeness of community stakeholders, logistical challenges, inadequate priorities, and negative experience from previous studies were main barriers to effective engagement of communities in research. The facilitators entail effective community entry and engagement of stakeholders at beginning of the research, effective community engagement strategies, community empowerment, and community motivation. Ethical considerations in community engagement had to take into consideration the cultural specificities of respective communities, community autonomy, review of research protocols, informed consent, avoidance of community exploitation, ensuring fidelity and trust, proper communication regarding risks and benefits, and privacy and confidentiality.Co-creation of project through recruitment and training of community volunteers using mostly youths as co-researchers on the research projects could play a major role in building a community feeling of ownership of the projects, therefore addressing doubts that could have existed regarding the research and the institutions involved . The rolGeographical/spatial limitation was identified in our review as a barrier that affects effective community engagement. This observation is congruent with previous studies that noted similar observations ,64. We nDespite the barriers highlighted in our review, we observed that there were several facilitators that promote community engagement in research. These were noteworthy: effective engagement of stakeholders at beginning of the research, culture sensitive community engagement strategies, and community empowerment and community motivation. Engaging key stakeholders especially the traditional and religious leaders and community-level government representatives at the beginning of the research projects by research institutions or individuals is pivotal for the success of any research enterprise. In settings in SSA where local leaders  are much revered by the general populace or their followers, meeting with community and political leaders who are in charge of the governing of communities is very crucial for the success of the engagement. This could be ascribed to the influence the leaders have in facilitating relationship and trust building between the research institution/team and the population therefore providing fertile ground for effective engagement ,82-88. Cet al. [The employment of effective community engagement strategies including two-way communication with communities (leaders and community members), openly acknowledging the role the entire community plays in the research, good cultural knowledge by researchers, effective use of existing social structures and networks in the communities facilitate community mobilization and engagement in the research. This finding of our review is compatible with findings from previous studies that urge researchers to employ effective engagement strategies to conquer the trust of the communities and facilitate community engagement -94. Dyeret al.  reportedet al. -98.Formation of community advisory boards (CAB) was also realized in our review as an important mechanism that facilitates effective community engagement. The CAB serves as a crucial liaison that facilitates communication and relations between the communities and the research institutions, therefore facilitating community engagement. CAB serves as community watchdog that help to identify community priorities and interests; identify community members to serve on project steering committees and promote community support for and involvement with research ,100. We Avoidance of exploitation by researchers is one key ethical issue regarding community engagement in research. Power imbalance between researchers and poorer communities leads to undue inducements pushing communities to participate research without fully understanding of risks and benefits, since they are attracted to monetary incentives that the project may come with, or from the fear of reprisal when they refuse to participate in the project . CABs coThe gender of field workers has influence on the engagement process as it determines the extent to which participants feel free to express themselves ,115. TheStrengths of the study: this review has ethical and gender considerations as central questions of the review. These issues have not been carefully assessed in previous reviews.Limitations of the study: notwithstanding the outlined strengths, some limitations are imminent. First, excluding commentaries, personal reports and papers that have not been published in English or French may result in the loss of important findings. Secondly, some key papers published before 2000 might have been missed.While there are useful practices currently adopted in engaging communities in research in SSA, a number of barriers militates against such engagement efforts which negatively affect the implementation of community-based research projects. Gender mainstreaming and ethical standards are reported but not optimally operationalized. It is relevant to come up with clear ethics and gender frameworks to guide community engagement in research in SSA.Meaningful community engagement is a major determinant of effective and meaningful research practice;Ethical and gender considerations are key in coming up with sustainable, inclusive and acceptable findings in research, relevant to evidence based health policy making;Context is an important consideration in effectively engaging communities in research.Gender mainstreaming is abundantly reported as relevant, but inadequately operationalized in the community engagement in research process;Ethical considerations are not reported in a clear and systematic manner;We propose a 5 level framework for effective community engagement in research .


Meniscal injuries caused by trauma, degeneration, osteoarthritis, or other diseases always result in severe joint pain and motor dysfunction. Due to the unique anatomy of the human meniscus, the damaged meniscus lacks the ability to repair itself. Moreover, current clinical treatments for meniscal injuries, including meniscal suturing or resection, have significant limitations and drawbacks. With developments in tissue engineering, biopolymer scaffolds have shown promise in meniscal injury repair. They act as templates for tissue repair and regeneration, interacting with surrounding cells and providing structural support for newly formed meniscal tissue. Biomaterials offer tremendous advantages in terms of biocompatibility, bioactivity, and modifiable mechanical and degradation kinetics. In this study, the preparation and composition of meniscal biopolymer scaffolds, as well as their properties, are summarized. The current status of research and future research prospects for meniscal biopolymer scaffolds are reviewed in terms of collagen, silk, hyaluronic acid, chitosan, and extracellular matrix (ECM) materials. Overall, such a comprehensive summary provides constructive suggestions for the development of meniscal biopolymer scaffolds in tissue engineering. Meniscal tear is one of the commonplace injuries of the knee joint, which is often caused by trauma, degeneration, and osteoarthritis . PartialThe repair capacity of the meniscus is related to the degree of vascular infiltration and structure. Compared to lateral edge of the meniscus, the medial edge lacks vascularity and therefore meniscus is less capable of self-repair. The complex anisotropic structure of meniscus increases the difficulty of self-repair. To adapt to compression, stretch, and torsion stresses of the knee from all directions at rest or during sports, the collagen arrangement of meniscus shows a gradient change. The continuous development of tissue engineering has made it possible to repair the meniscus perfectly. Tissue engineering can mimic the original natural tissue and stimulate the body’s regenerative potential to promote the growth of tissue into the scaffold and complete the gradual replacement to form functional tissue.Recent researches have found that biopolymer scaffolds have favorable development foreground in the repair of a variety of tissue injuries . They acThe meniscus is unique in that it manifests as discrete cartilage-like tissue during embryonic life and subsequently depends on its location to be shaped by different external environmental stimuli. Ultimately, the vascular formation and innervation would be affected to develop into different tissue stratum. Signal transduction, vascular formation, innervation, stem cell origin, and location in the body all produce subtle tissue development differences. These distinctions guide the subpopulations of cells that will ultimately make up the tissue .The capillary plexus surrounding the meniscus, which originates from the joint capsule and synovial tissue, provides 10–25% of the blood supply to the meniscus and is confined to the peripheral third of the meniscus . The menThe nerves and mechanoreceptors of the meniscus are mainly located in the anterior and posterior horns of the meniscus and the lateral two-thirds of the body. The medial third of the meniscus is thin and lacks nerves . This paThere is a significant difference in size between the lateral and medial meniscus in humans. The medial meniscus is C-shaped and covers 51%–74% of the area of the medial tibia plateau. The medial meniscus is slightly thinner in volume . It is mThe meniscus comprises cells and an extracellular matrix of collagen, proteoglycan, matrix glycoproteins, and elastin. The outer third of the Meniscus is dominated by fibroblasts and the inner third is by chondrocytes. The middle third of the meniscus has fibro chondrocytes . CollageTherefore, the meniscus is an anisotropic structure, which results in a low capacity for self-repair and the site of injury can influence the choice of treatment options for the orthopedic surgeon. According to the mechanism of injury, meniscal injuries can be classified as laminar, transverse, longitudinal, bucket handle, and oblique tears . Only inTissue engineering is the implantation of a scaffold loaded with cytokines or cells into tissue damage, and the gradual transformation of the scaffold into biological tissues, to achieve the purpose of repairing the damage. Scaffolds are the carriers of cytokines and cells. Therefore, as the key to tissue engineering, the selection of scaffold materials is very important. Compared with synthetic materials, natural materials have many significant advantages , such asHowever, homogeneous scaffolds are unable to meet the individualized repair of meniscus, so it is important to design scaffolds that properly guide meniscal repair according to the characteristics of each meniscal department. The fibrous arrangement of the natural meniscus should be simulated so that the meniscal scaffold can resist circumferential and radial stresses in the horizontal direction and compressive stresses in the vertical direction  Berni e. BahceciCollagen is the most abundant ECM protein, with biodegradability, low immunogenicity, and adequate sources. Collagen self-assembles into cross-striated fibers that provide support for cell growth and are responsible for the mechanical elasticity of connective tissue . Col I iCOL1A1, cartilage oligomeric matrix protein (COMP), Tenascin C (TNC), and Scleraxis (SCX) genes , synovial cells, and cells from the infrapatellar fat pad were seeded onto aligned electrospun Col I scaffolds and optionally encapsulated in a hydrogel . TreatmeX) genes . MeniscaX) genes , suggestX) genes in vitro for 3 weeks. Cell-seeded collagen scaffolds showed better integration of natural tissue compared to cell-free collagen scaffolds or the control group  silk meniscal scaffold system was designed to mimic the natural meniscal structure by inoculating the scaffold with chondrocytes, human fibroblasts, or adipose-derived stem cells in a spatial separation pattern similar to that of natural tissues 4) to MeHA, which had different gelling time, mechanical strengths, and degradation rates  to hyaluronan by EDC and mixed it with gelatin to obtain hydrogels mediated by tyrosinase (TYR) cross-linking. Compared to gelatine alone, mixtures of HA and gelatine in the presence of TYR have faster gel transformation time and higher mechanical properties, and the mechanical peculiarities and degradation kinetics were regulated by TA substitution and TYR concentration  is a GAG consisting of the repeating disaccharide portion of d-glucuronic acid and N-acetyl-d-glucosamine and is found in large amounts in the skin and musculoskeletal tissues. Hyaluronic acid has been widely used in tissue regeneration and medicine due to its superior physiological function and biocompatibility. It also has a well-controlled degradation rate and mechanical properties. HA alone has a relatively fast degradation rate and weak mechanical strength, and the most common modification method is the reaction of methacrylic anhydride with HA to form methacrylated hyaluronic acid (MeHA), which has photocrosslinking properties . The phoon rates . In addion rates . Kim et ntration .Ghodbane et al. injected collagen HA sponge as an extracellular matrix into the meniscal scaffold, which matched the circumferential tensile and axial compressive properties of the natural meniscus and had appropriate porosity , and MeHA, hybrid hydrogels, and 3D printed PCL scaffolds, and then evaluated the potential for ex vivo meniscal regeneration under dynamic compression. The results showed that hydrogels had a higher potential for meniscal regeneration compared to PCL, with agarose and MeHA favoring the regeneration of the inner meniscal region and gelatin favoring the regeneration of the outer meniscal region.  to the fibermesh were also investigated, in which the softer MeHA fibermesh was susceptible to deformation and densification by cell traction, whereas the stiffer MeHA fibrous network supported more MFC invasion when placed near the meniscal tissue  is a biopolymer made by deacetylation of chitin with a structure similar to GAG. CS has a wide range of applications in biomedical fields due to its splendid biodegradability, bioactivity, and biocompatibility. CS can provide active sites for cell adhesion, cell-cell, and cell-matrix interactions, which in turn plays an important role in regulating cell proliferation and function. The cationic property of CS allows for the immobilization of negatively charged enzymes, proteins, GAGs, polysaccharides, or other negatively charged molecules under mildly acidic conditions . CS can response . The molresponse .Sarem M et al. prepared chitosan/gelatin composite scaffolds exhibiting highly inter-connected pore architecture with swelling and degradation behavior using genipin as a biocompatible cross-linking agent. Gelatin improves the biocompatibility of CS, and gelatin/chitosan scaffolds have excellent compatibility with meniscus-derived cells  were prepared and tested for their effectiveness in promoting meniscal repair by migrating endogenous meniscus cells from the surrounding meniscus or exogenously seeded hBMSCs. Both endogenous meniscus cells and hBMSCs permeated into the MDM scaffold. In the absence of exogenous cells, 8% of the MDM scaffold promoted the overall repair of meniscal defects in vitro  Continuing to optimise the materials used in the preparation of meniscal scaffolds; 2) A bionic integrated meniscus prosthesis based on the differences in the various regions of the meniscus; 3) In-depth study of the mechanism of differentiation of stem cells into different cell phenotypes of the meniscus ; 4) Observe the long-term repair effect of the meniscus scaffold implantation.


Economic sustainability involves the development of an organisation that meets its future needs through an integrated policy, planning, and social learning process. The purpose of this study was to investigate the mediating role of competitive advantage in the relationship between strategic orientation and economic sustainability under unpredictable circumstances. This study collected quantitative data from a total of 284 halal small and medium enterprises (SMEs) from Indonesia through structured interviews. Data were analysed using partial least squares structural equation modelling (PLS-SEM). Moreover, this study adopted artificial neural network (ANN) analysis for a model-free estimation using non-linear, multilayer, and parallel regression. The results revealed statistically significant and positive effect of strategic orientation on economic sustainability. Additionally, this study found that competitive advantage expanded the effect of strategic orientation on economic sustainability. Findings of ANN analysis confirm high prediction accuracy of the model. Findings of the sensitivity analysis highlighted the importance of innovation, network and technological orientation, and the positive effect of competitive advantage on halal SMEs economic sustainability. In order to achieve long-term economic sustainability, halal SMEs should therefore focus on innovation capacity, vertical and horizontal networking and adoption of the latest technologies. The uniqueness of this study focused on the strategic orientation and value of competitive advantage of halal SMEs towards economic sustainability. Additionally, this study was the first to develop hybrid SEM–neural network analysis to apply sensitivity analysis for the evaluation of the contribution of each exogenous predictor towards the endogenous construct. Indonesia Maju) is one of the government’s initiatives to support sustainability development. Shariah economy and finance  have been identified as key contributors considering that the vast global opportunity of $1.9 trillion in 2020 and domestic opportunity of $184 billion in the related consumer spending market have not been fully tapped. Indonesia is the largest domestic halal economy market, by 87.0% of the total population or about 236.53 million people. This amount is equivalent to 12.7% of the entire Muslim population in the world. The halal economy has remained more unscathed by the effects of the COVID-19 pandemic than the national economy, with a contraction of − 1.70%, as compared to − 2.07% for the national economy in 2020 .The environmental system of an economy is the central factor to gain business opportunities for sustainable development. The concept of sustainability and the interdependence of the economy and environment are increasingly important for policymakers. Small and medium enterprises (SMEs) play essential roles of contributing to the economic growth of developing countries and creating income and job creation; however, numerous small business entrepreneurs face failure , which was proposed by Penrose , is the This study argued that strategic orientation enhances halal SMEs’ competitive advantage in a hyper-competitive environment. Thus, this study attempted to explore and develop a framework of developing hybrid SEM–neural network analysis on how customer orientation, competitor orientation, technology orientation, network orientation, and innovation orientation affect the economic sustainability of halal SMEs through competitive advantage in Indonesia. The above problem statements and the lack of sufficient findings on the related areas prompted the current study to contribute to the existing body of knowledge and address other gaps, such as the inconsistent findings on the relationship between strategic orientation and economic sustainability in related literature.In this study, RBV was captured with respect to strategic decision-making orientation and competitive advantage towards the economic sustainability of halal SMEs in Indonesia. This study designed, developed, and validated an instrument to measure the dimensions of strategic orientation, competitive advantage, and economic sustainability using the hybrid SEM–neural network analysis.RBV (a bona fide theory), which was introduced by Penrose , emphasiBarney  observedMoreover, with respect to emerging markets, studies on RBV have suggested that local firms are interested in using foreign alliances to acquire advantages over their domestic rivals, in emphasising the importance of network ties as an intangible resource for entrepreneurial start-ups, and in understanding the changing benefits of unrelated diversification as economic institutions develop Barney, . The gloBarney  stressedThe concept of the triple helix model was originally proposed by Etzkowitz and Leydesdorff . TheoretFurthermore, Carayannis and Campbell  added a The current study focused on balancing development and sustainability by addressing both innovation and sustainability by modifying the original triple helix model. This study considered the triple helix concept within the context of halal SMEs, specifically in terms of their economic sustainability, towards achieving innovation and sustainability in a hyper-competition setting. There is an increasing awareness that a knowledge-based society operates according to a different set of dynamics, as compared to an industrial society, with an emphasis on SMEs. Knowledge-based innovations are more closely linked to sources of new knowledge and human resources. Fostering a continuous process of the formation of halal SMEs based on advanced technologies moves to the heart of strategy orientation.Additionally, this study supported the quadruple and quintuple innovation helix to change its spin as the production of new knowledge and technology, which has become an increasingly important element for the performance of halal SMEs. This can also drive the sustainability of halal SMEs towards meeting the global and local knowledge economy and society through strategy, democracy of knowledge, and innovation. At this level of the quadruple and quintuple innovation helix, the enhancement of the performance of SMEs and other knowledge-producing institutions often becomes the key issue. The concept of democracy of knowledge, ecology, and society is crucial for halal SMEs to obtain innovation. Sustainable development, progress, and performance across different dimensions of halal SMEs explain the success of quadruple helix.Competitive advantage can be sustained by generating innovative ideas, quick response to customers’ needs, and development of new beneficial products for customers  was employed in this study to assess the complex cause–effect relationships  . Thus, H1a was supported. The present study supported the study by Lee et al. , which supported H1b. Besides that, competitor orientation was found to exhibit significant and positive influence on competitive advantage (H2a)  and economic sustainability (H2b) . These findings were found to be consistent with the findings reported by Tseng et al.  and economic sustainability (H3b) . In other words, H3a and H3b were accepted. Park and Zhang  and economic sustainability (H4b) . These results supported both H4a and H4b. This study also demonstrated the significant and positive influence of innovation orientation on both competitive advantage (H5a)  and economic sustainability (H5b) . This present study supported the study of Haffar et al.  . Thus, H6 was accepted. Desiana et al.  was calculated according to the criterion suggested by Cohen  of all factors at the individual level (single factor). Referring to Table Next, effect size . Moreover, competitive advantage mediated the relationship between competitor orientation and economic sustainability . Similarly, competitive advantage mediated the relationship between technology orientation and economic sustainability  and the relationship between network orientation and economic sustainability . Finally, this study also demonstrated the mediation effect of competitive advantage on the relationship between innovation orientation and economic sustainability . Table The obtained results of this study revealed the mediation effect of competitive advantage on the relationship between customer orientation and economic sustainability  values for training and testing  and economic sustainability of halal SMEs. This study proposed RBV to explain the roles of halal SME owners’ capabilities of implementing strategic orientation and competitive advantage towards economic sustainability in this highly competitive market Barney, . The resThis study demonstrated the significant influence of strategic orientation on economic sustainability of halal SMEs. The results of this study confirmed the significant mediating role of competitive advantage in increasing the performance and promoting economic sustainability among halal SMEs. Similarly, Deyganto  found thBesides that, this study found the positive and significant influence of technology orientation on competitive advantage and sustainability. Technological and innovative activities and the potential for both radical and incremental changes are central for the sustainability of halal SMEs. This study also found the significant influence of technology orientation on economic sustainability, such as technological superiority to differentiate new products. This study supported the findings of Park and Zhang  on technThis study demonstrated the significant and positive influence of innovation orientation on competitive advantage and economic sustainability. Desiana et al.  showed tFurthermore, this study argued that competitive advantage is a crucial factor in the relationship between strategic orientation and economic sustainability. Theoretically, the integration of competitive advantage as a mediator in this study extended the RBV theory and literature on dynamic capability. This study concluded the significant role of competitive advantage in mediating the relationship between strategic orientation and economic sustainability. Additionally, the current study extended the halal entrepreneurship literature through human network, network capability, and competitive advantage in the digitalisation era. Besides that, this study demonstrated the mediating role of competitive advantage. Halal SMEs need to recognise the importance of competitive advantage by transforming new systems in manufacturing, product delivery system, and online sales platform of halal products in order to accomplish strategic diversification and innovation . The quadruple and quintuple innovation helix concepts  are two important basic theories that explain strategic orientation, competitive advantage, and economic sustainability of halal SMEs. This study developed RBV through competitive advantage as a mediator, and this study found that all constructs increase the economy sustainability of halal entrepreneurship. Competitive orientation, customer orientation, competitor orientation, network orientation, innovation orientation, and technological turbulence can adequately improve the survival and sustenance of halal enterprises into an unforeseeable future. Resource capability and competitive advantage can improve the efficiency of enterprises. Strategic orientation is an attribute that can adequately improve the competitive advantage of halal enterprises. Moreover, the quadruple and quintuple innovation helix concepts explain the significant roles of environment, policy, and knowledge for SMEs to gain sustainability. The democracy of innovation, knowledge, and strategy help halal SMEs to expand their market and position in hyper-competitive market.This study offered several recommendations for halal small businesses to remain sustainable or competitive through strategy orientation. The study also presented relevant recommendations for policymakers and other concerned bodies. Based on the findings of this study, innovation, customer, competitor, network, innovation, and competitive intensity are critical in determining the robustness of resource capability. These aspects adequately improve the growth of sales and the survival and sustenance of halal enterprises into an unforeseeable future, as well as the efficiency of enterprises and competitive advantage of halal enterprises, particularly in trying to be different from other competitors. Additionally, decisions on the survival of enterprises into an unforeseeable future, resource capability of competitive advantage and environmental turbulence should be prioritised. Finally, when it comes to the decisions on economic sustainability, resource capability of strategic orientation should be the main focus.This present study’s findings also contribute to the social environment. Halal SMEs should focus on strategic orientation by combining internal resources (innovation and network) and external resources (customer orientation and competitor orientation) to gain competitiveness and sustainability. Secondly, customers have been increasingly aware with healthy consumption and habit of purchasing halal products. Consuming halal products can create an eco-friendly system that creates positive life circumstances.Additionally, this study suggested a few policies. Firstly, the regulation maker of halal certification (Islamic Council of Indonesia) serves as an important strategic institution for sustainability by proposing and educating customers to consume healthy and halal products. Secondly, education is a central plot for new start-ups to obtain entrepreneurial knowledge and training. Thirdly, the government should provide infrastructure development and policies of halal products, which focus on innovation, competition, and growth of SMEs, for halal enterprises to make significant contributions towards economic sustainability. Additionally, the government can support halal SMEs to invest in modern production facilities  in order to have capabilities and capacities of local industries that meet international quality standards, resulting in more halal SMEs that are able to enter new export markets. Moreover, the government, society, and SMEs should increase knowledge, innovation, and culture change to gain their market share locally and globally and expand the performance and economic sustainability of SMEs.This study also recommended that science and halal SMEs focus on implementing strategies, as these strategies facilitate SME managers or owners to design, develop, and enhance resource-based approach and capabilities. With respect to the quadruple and quintuple innovation helix concepts, establishing science and knowledge in universities can be helpful for quicker exchanges or interactions of strategies and capabilities among universities, industries, the government, and actors of SMEs. Last but not the least, the developed questionnaire in this study served as a tool to discover shortcomings and deficiencies in the path of promoting sustainability in science and SMEs.Overall, policy, education and training, and infrastructure development should focus on halal SME innovation, competition, and sustainability for halal enterprises to make significant contributions towards social implementation.This study encountered a few limitations. Cross-sectional data were obtained from 284 halal SMEs in Indonesia. Thus, a larger sample is recommended for future research to generalise and better understand the implementation of strategic orientation and policy decision-making for halal SMEs. Secondly, competitive orientation, customer orientation, competitor orientation, network orientation, innovation orientation, and technological orientation were employed in this study to explore the role of strategic orientation as well as the mediating role of competitive advantage. Additionally, the profitability and cost reduction were employed in this study to represent economic sustainability. Therefore, other indicators of economic sustainability can be implemented to achieve various outcomes. Lastly, the dynamic capability approach can be explored in relation to the economic sustainability of halal enterprises in developing and developed countries.


The surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the “parasuprasellar” area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area.Surgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area.The EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone  removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series.The EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON. With advances in surgical anatomy and endoscopic technology, the endoscopic endonasal approach (EEA) has been widely applied for ventral skull base lesions over the last several decades –3. FurthAlthough not common, some different pathologies can afflict these regions, including primary lesions, such as ACP meningiomas and paraclinoid aneurysms, but more secondary tumors spread, such as tuberculum sellae meningiomas, invasive pituitary adenomas and craniopharyngiomas, from nearby regions. Pathologies encountered in these areas are typically intra- and extracranially. Moreover, these lesions tend to displace the ON from above and/or below, erode osseous and dural structures, and even encase the ICA and its bifurcation. Therefore, effective resection of these lesions poses a considerable challenge, even for skilled and experienced neurosurgeons.Several traditional transcranial approaches (TCAs), including the standard or extended pterional approach , 13, orbIn contrast, the EEA provides a direct corridor to access extradural lesions, with the advantage of easy removal of extensively involved osseous architectures and dural attachments. Additionally, a corridor to the subdural lesion is established when the lesion is removed. Most importantly, EEA allows for early identification and control of the paraclinoidal ICA, which is the main structure that must be crossed to expand laterally into these regions. These advantages are particularly promising for treating lesions involving these areas. Nevertheless, there are few reports regarding the endoscopic anatomy and how to effectively manage lesions involved these areas , 11.For this reason, we sought to undertake a thorough anatomical description of the lateral aspect of the planum sphenoidale and the tight junction region of the OC, ACP, and ICA and its dural rings. These regions are located in the lateral area of the suprasellar region, the “parasuprasellar” area. Building on our detailed dissection, we introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area. Indications and nuances of these approaches in treating 12 patients with tumors and aneurysms involving this area are also presented.Five embalmed and injected adult cadaveric heads were used for endoscopic and microsurgical dissection. The anatomy research was approved by our institutional ethics committee. Endoscopic endonasal anatomical dissections were performed using rod lens endoscopes . An extended EEA to the sella, parasellar and suprasellar areas, involving wide sphenoidotomy, posterior ethmoidectomy, and posterior septectomy, followed by a transpterygoid approach, was performed for all cadaveric heads in a stepwise manner, as previously described , 3, 16. We defined the parasuprasellar area as a quadrangular space, and its main contents included the ON, the ICA and its proximal and distal dural rings, the ophthalmic artery (OA), and the ACP. The PEA is defined as the upper boundary of the parasuprasellar area. The inferior boundary is formed by the horizontal connection between the inferior edge of the LOCR and MOCR. The medial boundary is the vertical connection between the medial edge of the MOCR and the PEA, and the lateral boundary is the vertical connection between the lateral edge of the LOCR and the PEA. In addition, we divided the parasuprasellar area into 2 compartments based upon the ON: supraoptic and infraoptic compartments . All patients also underwent preoperative thin-slice CT scans to evaluate the extent of OC and ACP involvement. Preoperative BOT was performed to evaluate whether collateral circulation could be compensated; if poor, an endovascular stent or bypass would be prepared. Intraoperative electrophysiological monitoring, particularly visual evoked potentials (VEP), was used routinely throughout the procedure. Intraoperative neuronavigation and Doppler ultrasound were also applied to determine the exact course of the ICA. Additionally, the paraclival ICA was exposed in advance for proximal control. Special attention was given to the ophthalmological evaluation, including visual acuity and visual field, and limitations of ocular motility were observed by an ophthalmologist for all patients preoperatively and 3 to 6 months postoperatively. All medical records, including symptoms, neuroimaging, intraoperative videos, technical nuances, and surgical outcomes, were reviewed and analyzed retrospectively , and 1 patient developed postoperative panhypopituitarism, which normalized by the 3-month follow-up. One patient experienced permanent DI and hypothyroidism, and postoperative hormone replacement therapy was required in the follow-up period. Postoperative cerebrospinal fluid (CSF) leakage occurred in 1 patient, and endoscopic endonasal repair was performed. Postoperative oculomotor nerve palsy developed in 2 patients; fortunately, it resolved completely in one patient by the 1-month follow-up, and significantly improved in the other patient by the 6-month follow-up. No postoperative intracranial infection or ICA injury occurred in this series.The EESO and EEIO approaches were successfully performed either alone or in combination for 12 patients harboring tumors and aneurysms involving the parasuprasellar area . For example, the transtuberculum/transplanum approach can be conveniently combined with the single EESO approach to provide better access to anterior cranial fossa meningiomas with lateral extension (case 1). Similarly, the combination of the transcavernous approach and EEIO approach has the potential for achieving complete resection of ACP meningiomas or pituitary adenomas involving the CS . The EESO and EEIO approaches can be used as a complement to the midline approach and transcavernous approach and are extremely useful to access extensive pathologies for more complete resection while limiting morbidity.Since the EESO and EEIO approaches require extensive removal of the skull base, strict cranial base reconstruction techniques for closure of the osteodural defect should be discussed. In our institution, we first use small pieces of autologous fat for intradural closure to eliminate the dead space. Then, we adopted the so-called sandwich technique, that is, two pieces of fascia lata or artificial dura were placed between the dura and bone as inlay substitutions and outside the bone as outlay substitutions, respectively. Finally, a vascularized pedicle nasoseptal flap harvested at the beginning of the procedure was positioned to cover the cranial defect, and each of the above layers was fixed with biological fibrin glue. However, it must be emphasized that, in the most lateral region of the cranial defect (where the ON stands), an inlay-overlay of dural substitutes will be difficult due to the irregularity of the osteodural defect. Therefore, autologous fat pieces should be placed across the intraextradural space.In our practice, the EEIO is a graduated, stepwise approach based largely on the lesion location, size and extent. Our anatomical study and clinical cases demonstrate how to assemble multiple surgical corridors to provide personalized access to complex parasuprasellar lesions. In Case 10, in which the left paraclinoid aneurysm was located just below the ON, successful clipping of the aneurysm was achieved using a pure EEIO approach , the Ganpo555 Engineering Excellence of Jiangxi Science and Technology Department (2013), and the Key Research and Invention Plan of Jiangxi Science and Technology Department (20192BBG70026).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed. CKD is defined by the Kidney Disease Outcomes Quality Initiative in terms of either kidney damage or decreased glomerular filtration rate  and produces Blood (the body circulation) . TherefoBesides, the vital substances stored in the kidneys depend on the transportation and distribution of the spleen. The disorder of spleen transport is usually caused by improper diet, deficiency of endowment, and excessive fatigue, which lead to spleen Qi deficiency. Furthermore, with the development of spleen Qi deficiency, the development of disease, the decline of fire in the vital gate, and the loss of warm spleen, it will further lead to the deficiency of spleen Yang. The spleen cannot warm the grain and liquid, and then the transport of liquid and water is abnormal, which leads to water dampness. As mentioned in “Plain Questions,” with Yin and Yang in relative balance, the spirit can be cured. Thus, TCM believes that “spleen-kidney deficiency” is an internal condition; blood stasis, internal dampness, and heat are inextricably linked to the patient’s viscera . The treThe pathogen of CKD is mainly manifested as blood stasis, dampness heat (hygropyrexia), and turbid toxin (retained hazardous substances). Blood stasis syndrome is one of the most common CM syndromes among patients with primary glomerular disease . “Blood When the spleen and kidneys are deficient, water dampness is endogenous. Pathogenic dampness resides in the body, leading to heat from Yang, or heat from dietary intake, and eventually pathogenic dampness changes to heat from dampness. As the famous medical scientist Lingtai Xu inferred, there must be heat when there is dampness. In microscopic differentiation of syndromes, dampness heat in renal pathology often shows swelling of endothelial cells, formation of microthrombus, narrowing of the capillary lumen, and release of inflammatory mediators . The theAccording to the long-term clinical practice, different CMMs have different pharmacological effects and are endowed with different TCM efficacies. Previous studies have shown that in patients with CKD stage 3 with different TCM syndrome patterns, four different therapies including invigorating Qi and Blood, promoting blood flow, expelling wind-evil (a kind of exogenous pathogenic factors), and clearing heat and dissipating dampness (regulating the immune system and promoting urination) significantly improved the glomerular filtration rate and decreased proteinuria . This reThe difference between TCM and modern medicine is that it has the significant property of being multicomponent. Single CMM is a unit that contains the least amount of components in TCM, and the pharmacodynamic material basis has been studied most deeply. With the continuous progress of research, the mechanism of single CMM or CMM extracts for CKD is gradually been clarified.Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. In the clinical practice of TCM, AR is mainly used to invigorate Qi, manifested in two aspects, supplementing the Defense-Qi  and replenishing the Middle-Qi (which is the function motivity of spleen and stomach)  is derived from the dry roots of stomach) . Therefostomach) .The effects of AR on the reduction of proteinuria and serum creatinine have been studied in patients. After treatment with AR injection in 30 patients with chronic glomerulonephritis, the content of urine protein decreased obviously from 2328 ± 3157 to 1017 ± 765 mg/24 h . The eff4 and upregulated CD8 in patients with chronic glomerulonephritis, suggesting that it has a regulatory effect on cellular immunology  and MMP-9 (via its specific receptor c-met and inhibiting the phospho-p38 mitogen-activated protein kinase (MAPK) signal pathway  and suppressed the cytoskeletal rearrangement, improving the migration ability of podocytes nd MMP-9 . The mos pathway . Calycos pathway .Rheum palmatum L., Rheum tanguticum Maxim. Ex Balf., or Rheum officinale Baill, is widely used as a laxative for many years. Pharmacological studies have confirmed its multiple activities, such as antibacterial, purgative, antifibrosis, regulating gastrointestinal, antiinflammatory, and antitumor activities , the dried roots and rhizomes of tivities . In a sytivities . In additivities .As shown by Zhang et al., treatment with the extracts of RRR reversed the abnormalities of the urinary metabolites in adenine-induced CKD animals and reduced the expression of histopathological inflammatory markers such as collagen (Col) I, Col III, and pro-fibrosis marker TGF-β1 . Researcvia reversing aberrant DNA methyltransferases expression, thus upregulating the expression of Klotho protein  mice, rhein effectively recovered Klotho promoter hypermethylation  protein . Besides protein .Abelmoschus manihot (L.) Medic., a single medicament of TCM for eliminating heat and dampness, has been widely used for the treatment of CKD in China. As a modern preparation extracted from AC, the Huangkui capsule has been approved by the China National Medical Products Administration (Z19990040). As reviewed by Sun et al., in approximately 2,000 CKD patients, AC showed to decrease proteinuria with stable kidney function during follow-up , the flower of ollow-up . Besidesollow-up .via adjusting METTL3-dependent m6A modification and regulating NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling  is a CMM derived from the root of g stasis . Previoug stasis .In the study of metabonomics in rats with CRF, 54 metabolites could be regulated by SM ethanol extract and water extract . MoreoveSeveral components isolated from SM have been used to treat kidney disease. The pharmacodynamic effects of salvianolic acid A on 5/6Nx rats showed that it could reduce proteinuria, improve renal function, and reduce renal tubulointerstitial fibrosis. The mechanism is closely related to its antiinflammatory activities through inhibition of the activation of the NF-κB and p38 MAPK signaling pathways . In addiIn general, the effect of SM on promoting blood circulation and removing stasis may be related to the increase in renal blood flow, the decrease of the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF), and the recovery of expression of neuronal nitric oxide synthase (nNOS) by magnesium lithospermate B . On the Poria cocos (Schw.) Wolf (Polyporaceae). The inner parts of Poria are commonly known as “Fuling” in Chinese. Triterpenoids are the main components of Poria, and it exhibits a variety of biological activities such as antiinflammatory, immunomodulatory, antitumor, antioxidant, and antibacterial activities  is the dry sclerotium derived from tivities . In TCM,tivities . Likewistivities . An in vEBP mRNA . Its effin vivo and in vitro  are the most basic composition units, the simplest form of multi-CMM formula, and a centralized representative of CMM compatibility . It is nAngelica sinensis (Oliv.) Diels) are a common CMM pair used to treat kidney disease for years. The combination of the two CMMs is also known as Danggui Buxue Tang (DBT) with a weight ratio of 5:1. When the two CMMs are decocted together, it can help a better dissolution of effective components and the generation of new components. For example, with the increase in the ratio of AR, the dissolution of ferulic acid and ligustilide increased  mRNA expression and secretion of EPO protein , preventing the activation of c-Jun N-terminal kinase (JNK)-MAPK, and inhibiting the expression of NLRP3 inflammasomes . IntegraPanax notoginseng (Burk.) F.H.Chen), is a patented hospital preparation, which was designed and developed by the famous nephrologist Nizhi Yang , composed of AR and Notoginseng Radix et Rhizoma  is a classical CMM formula originally from an ancient medicinal book “Treatise on Febrile Diseases.” It is composed of Aconiti Lateralis Radix Praeparata (Fuzi), Poria, Atractylodis Macrocephalae Rhizoma (Baizhu), Paeoniae Radix Alba (Baishao), and Zingiberis Rhizoma Recens (Shengjiang). ZWT has been widely used as a remedy for CKD, relieving the clinical manifestations of edema, dyuria, and oliguria through warming Kidney/Spleen Yang to promote diuresis. Clinical studies have indicated that ZWT improved the clinical curative effect, alleviated the scores of symptoms such as the limb chills, decreased proteinuria, and blood lipids, improved renal function, and alleviated serum levels of IL-8, IL-13, CTGF, and hepatocyte growth factor .The warming Yang effect of ZWT is related to antiinflammation and antifibrosis. In improving the inflammatory response, ZWT significantly reduced the serum levels of AGEs and decreased the release of inflammatory mediators  . The mec+ and K+ and keeping the balance of water and the electrolyte content ; on the other hand, patients with chronic nephritis are often combined with the exogenous wind-heat syndromes, damp-heat syndromes, and blood stasis syndromes, which should be treated by clearing heat and removing dampness, as well as promoting blood circulation and removing blood stasis . TherefoAs an empirical formula, YQQRG is composed of 12 CMMs. The prescription takes AR as the monarch medicine, combined with Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (Fangfeng), which is the composition of Yupingfeng San, to invigorate Qi, consolidate the superficial resistance, and eliminate evil or toxin in the outside; Lonicerae Japonicae Flos (Jinyinhua), Forsythiae Fructus (Lianqiao), Duchesneae Indicae (Shemei), Hedyotis Diffusa (Baihuasheshecao), and Imperatae Rhizoma (Baimaogen) can clear heat and remove dampness in the inside; Poria, Alismatis Rhizoma (Zexie), Leonuri Herba (Yimucao), and Dioscoreae Nipponica Rhizoma (Chuanshanlong) can promote blood circulation and diuresis and guide the evil of dampness, heat, and turbid to go out. In a previous clinical study, it was found that YQQRG could significantly reduce TCM symptom scores of patients with chronic glomerulonephritis, effectively decrease 24 h urine protein, and improve plasma albumin and immunoglobulin (Ig) G, IgA levels, and the effective rate of treatment was 90% .in vitro experiment indicated that treatment with serum-containing YQQRG inhibited LPS-induced rat mesangial cell proliferation, downregulated mRNA and protein levels of Wnt4 and TGF-β1, and reduced the aggregation of the mesangial matrix  and slit diaphragm proteins (CD2AP) , increaspression . The regUremic clearance granule (UCG) is the first CMM preparation in the field of treating early and mid-stage CRF. It contains 16 kinds of CMMs and exerts the effects of removing turbidity by catharsis, invigorating the spleen, dispelling dampness, promoting blood circulation, and removing blood stasis in TCM. In some small-scale clinical trials, UCG is effective in reducing serum creatinine levels, improving renal blood flow, and improving the state of microinflammation . In a muin vivo and in vitro  was formed. HGF is composed of RRR, Zingiberis Rhizoma, Bupleuri Radix, Glycyrrhizae Radix et Rhizoma, and Aconiti Lateralis Radix Preparata. It can significantly improve the renal function of rats in CRF models, reduce oxidative stress injury, and delay the development of renal fibrosis . At presThe above systematically summarizes the research strategies and mechanisms of TCM in treating CKD , but also regulate other factors toward normal from different links and the balance of Yin and Yang.1) The current clinical evidence, even from the meta-analysis, is not enough to support the clinical application of CMMs in kidney disease. More large-scale clinical trials are needed to assess the efficacy, effectiveness, and toxicity of CMMs to optimize their therapeutic and preventive potential. 2) The therapeutic effects of CMMs are attributed to their unique multitarget and multipath effects that are difficult to separate from the different stages of CKD. Therefore, when to use CMM and what kind of efficacy of CMM should be selected mainly depend on clinicians’ self-experience. It is urgent to construct modern pharmacological indicators to characterize the conditions for the application of CMMs, to facilitate the globalization of the application of CMMs. 3) Different prescriptions of TCM have different therapeutic characteristics, but there are few specific indicators that can reflect the action characteristics of TCM. It is necessary to clarify the scientific connotation of TCM with clear pharmacological indexes. 4) The multitarget mechanism of the TCM therapy has not been fully elucidated, and most of them are based on a single pathway. However, the interaction relationship between different signaling pathways is not clear yet, and the cross-targets among the pathways are rarely studied. It is necessary to deeply explore the mechanism and the interaction relationship of TCM in a multidisciplinary way and visualize the multitargets and multilink network of CMMs. 5) Currently, some ingredients derived from CMMs also show good efficacy, but it is unclear which ingredient has the best efficacy or which one is the most effective among CMMs and their ingredients. A well-designed randomized controlled trial is needed to confirm the efficacy and safety of potential drugs.However, there are still some issues that need to be resolved. in vitro studies. The effectiveness of CMM is the result of long-term clinical practice under the guidance of the TCM theory, which seeks to “reinforce deficiency and purge excess” through the synergistic effect of multitargets and multipaths. CMMs can not only inhibit the activation of myofibroblasts, the infiltration of inflammatory cells, the transdifferentiation of epithelial cells to mesenchymal cells, and the excessive deposition of ECM to improve renal fibrosis through various mechanisms, but also improve blood flow, inhibit the proliferation of glomerular cells and the accumulation of solutes, and relieve water retention to achieve a relative balance between Yin and Yang, which highlights the advantages of holistic control of TCM and provides a good therapeutic strategy for clinical treatment of CKD. Further research should focus more attention to large-scale clinical trials and combine the TCM theory with the latest medical research to deeply explore its mechanism, which is of great significance for TCM treatment of CKD.In summary, TCM has made major progress in the treatment of CKD and has shown a beneficial role in delaying CKD in clinical, animal, and


UAV-based object detection has recently attracted a lot of attention due to its diverse applications. Most of the existing convolution neural network based object detection models can perform well in common object detection cases. However, due to the fact that objects in UAV images are spatially distributed in a very dense manner, these methods have limited performance for UAV-based object detection. In this paper, we propose a novel transformer-based object detection model to improve the accuracy of object detection in UAV images. To detect dense objects competently, an advanced foreground enhancement attention Swin Transformer (FEA-Swin) framework is designed by integrating context information into the original backbone of a Swin Transformer. Moreover, to avoid the loss of information of small objects, an improved weighted bidirectional feature pyramid network (BiFPN) is presented by designing the skip connection operation. The proposed method aggregates feature maps from four stages and keeps abundant information of small objects. Specifically, to balance the detection accuracy and efficiency, we introduce an efficient neck of the BiFPN network by removing a redundant network layer. Experimental results on both public datasets and a self-made dataset demonstrate the performance of our method compared to the state-of-the-art methods in terms of detection accuracy. Object detection is the process of localizing and classifying objects in an image. It is an essential task in the computer vision field and attracts much interest from both the academic and industrial communities. Inspired by the success of deep learning (DL), the performance of object detection has been dramatically improved. With the development of various technologies, unmanned aerial vehicle (UAV) platforms are widely used in the remote sensing field because of their attractive proprieties, including high flexibility, ecological benefits, and so on.Object detection plays a pivotal role in many UAV applications, such as hazard monitoring , intelliFor a prolonged period, convolutional neural networks (CNNs) have been the dominant player in object detection. Numerous impressive object detection approaches have been proposed, such as R-CNN , Faster Recently, the Transformer network provides qualitative performance in the field of computer vision. It is worth mentioning that the Vision Transformer (ViT)  network First, by revisiting the object detectors for aerial images, we uncovered a potential problem: extracting the correlation information between contexts is urgently needed ,32,33,34Second, the neck is the key element in the target detection framework that carries on from top to bottom. It reprocesses and rationally utilizes the important features extracted from the backbone to facilitate the next step of the head for concrete task learning. The most common current use of the neck is BiFPN . Low-levTo summarize, the contribution of this article is fourfold.To the extent we are aware, we are the first to introduce a foreground enhancement attention block (FEAB) in the original Swin-tiny backbone to bring more contextual information and learn more recognizable features and investigate its effectiveness in aerial image object detection tasks. Moreover, the FEAB module we introduced in the backbone can theoretically be inserted into other existing hierarchical vision transformers.We additionally propose a straightforward and efficient weighted bi-directional feature pyramid network (BiFPN) for efficiently fusing feature maps with context information from different stages of the encoder.We have created a self-collected dataset around the lab, which currently has 2000 images, targeting both pedestrians and vehicles, which we have annotated and made public. The download link is given at the end of this article.Finally, we provide an in-depth analysis of the impact of each of the two critical components in FEA-Swin on detection accuracy. Our proposed method achieves competitive performance metrics on the VisDrone, NWPU VHR-10, and our self-collected dataset, exceeding the best currently available universal models.Aiming to better understand and design aerial image target detection models, this section presents relevant work, including Vision Transformer, Swin Transformer, attention mechanism, and object detection in aerial images.Object detection is one of the fundamental problems in the field of computer vision. For a long time, due to many difficulties such as slow detection speed, insufficient generalization ability, and complicated manual feature design of traditional methods, target detection has not been widely implemented in practical scenes. In recent years, with the rapid development of artificial intelligence, emerging technologies represented by deep learning have made breakthroughs in computer vision, natural language processing, speech recognition, and other research fields by virtue of their excellent generalization ability. At the same time, driven by the wave of technology, UAVs have the advantages of long endurance, low power consumption, and real-time processing and transmission, which enriches the application of target detection on UAVs and makes them gradually become the focus of attention.UAV aerial images are characterized by complex backgrounds and small and dense targets due to the imaging perspective being different from natural scene images, which leads to even more challenges for target detection in aerial images . Due to ClusDet  proposesDMNet  leverageGLSAN  proposesUCGNet  proposesIn daily life, human eyesight quickly scans the global environment to obtain the target area to be focused on, which is generally known as the focus of attention, and then devotes more attentional resources to this area to obtain more detailed information about the target, while suppressing other useless information. Motivated by that phenomenon, attentional mechanisms were introduced to computer vision with great success.The attention mechanism is capable of focusing high weights on important information and low weights to ignore useless information, with the ability to dynamically adjust the weights, making the model more responsive to different situations.Attention mechanisms in computer vision are divided into six types, including the basic four: (1) temporal attention, (2) branch attention, (3) spatial attention, and (4) channel attention, versus a mixture of two: (5) combined temporal attention and spatial attention and (6) spatial attention and channel attention. The most commonly used of these are (3), (4), and (6). Several representative efforts are presented below.SENet : It pionNon-Local : It usesRAN : A residViT is the first visual detector that uses a pure transformer framework. ViT divides the input image into multiple patches (16 × 16), and then projects each patch into a fixed-length vector to feed the Transformer. The subsequent encoder operation is exactly the same as in the original Transformer. As the images are classified, a special token is added to the input sequence, and the output corresponding to this token is the final category projection.ViT proves that deep models built with pure self-attention blocks can also perform outstanding results in various vision tasks. However, ViT also has obvious limitations, such as huge data requirements, a limited number of stacked layers, and the inability to encode locations in the model itself.Regarding the application of Transformer from natural language processing to the computer vision field, the main adjustment is the scale of the visual image and the high-definition issue. Despite the huge sensation ViT has caused in the computer vision community, it is not perfect and still has some drawbacks. One of the most serious of these is the compatibility of ViT with high-resolution images, because its computation generates a quadratic complexity associated with the image size, leading to a high number of tokens and a very high computational effort for self-attention requirements.In this case, Swin Transformer introduces two key concepts to solve the problems faced by the original ViT, which are hierarchical feature mapping and windowed attention transformation. The model designs sliding windows to compute only the self-attention of all tokens inside that window to reduce the computational effort. At the same time, the hierarchical structure allows the model to have adaptive modeling with linear complexity for images of different scales. In fact, the name of Swin Transformer comes from “Shifted window Transformer,” and the most vital component of Swin Transformer is shown in We now give an overview of FEA-Swin. First, our proposed FEA-Swin adopts the classical backbone–neck–head architecture, and the overall framework is shown in The RGB image of size r blocks  stacked  position of the original input feature X.In this case, ith level and f stands for feature fusion method.Objects in aerial drone images are usually small and dense, and there are limitations in the feature representation capability of a single layer of backbone. Thus, in an effort to efficiently and quickly fuse different scale feature maps from different layers of the encoder, we demand an advanced feature fusion network. In general, the output feature map ith level.Currently, one of the state-of-the-art FPNs is the weighted bi-directional feature pyramid network (BiFPN), as shown in ith level input feature map of the first layer as According to the idea of BiFPN, when our work requires the input feature map to be four layers, then the structure shown in In this section, to evaluate the performance of our method, we perform several experiments on both public datasets and one self-collected dataset. We compare the proposed FEA-Swin with the state-of-the-art object detection systems, including Swin Transformer-tiny with FPN , one-staIn this paper, the proposed system is tested on two publicly available datasets  and mean average accuracy (mAP) as the evaluation to compare the accuracy of our method with other methods. AP is the average precision at 10 intersection over union (IoU) thresholds ranging from 0.5 to 0.95, with an equal division of 0.05 intervals. We counted ten categories of AP, and MAP is the average of all categories of AP. For all experimental results, we report the performance of the last epoch. It is specifically noted that our detection threshold of IoU is set at 0.6.We first compare our method on two public datasets. Similarly, In general, FEA-Swin can precisely detect densely packed objects of different scales, including small objects (such as pedestrians and bicycles) and large objects  without geometrically increasing the number of model parameters.In order to further understand the behavior of FEA-Swin, we implemented substantial ablation studies on the Visdrone dataset. We explored the influence of both BiFPN and FEAB components. The increments of mAP are list in We discuss the effect of hyperparameters in this section to verify the parameter independence of the proposed method. To obtain controls for the different hyperparameter groups, we manually modified the hyperparameter values and recorded them to observe the effects on the self-collected dataset. We chose batch size, optimizer type, and weight decay coefficient as the three hyperparameters that are the most likely to affect the detector performance metrics. The consequences of our tuning are shown in This paper presents a novel transformer framework to accurately detect dense objects in UAV images. We designed a novel foreground enhancement attention Swin Transformer (FEA-Swin) framework to integrate context information to detect dense objects competently. We also improved a weighted bidirectional feature pyramid network (BiFPN) by designing a skip connection operation to keep abundant information about small objects. In addition, an efficient neck of the BiFPN network was introduced to balance the detection accuracy and efficiency by removing a redundant network layer.Experiments show that the proposed object detection method can significantly improve the accuracy compared with state-of-the-art methods. Extensive ablation studies were conducted to further demonstrate the performance of the proposed method. In the future, we will explore both accurate and lightweight FEA-Swin in UAV object detection tasks.


Refractory Crohn's-like enterocutaneous fistula indicates the aggressive manifestation and lead to poor prognosis of patients. The development of multidisciplinary strategies for fistula administration largely subjects to the deficiency of animal model for disease remodeling and the underlying pathogenic mechanism. For the purpose, infected anal fistula model was conducted by BLV single-core electrolytic aluminum combined with dextran sodium sulfate. Notably, the inflammatory granulation tissue and inflammatory cell infiltration in the perianal tissue were arised on day 7 of the model by utilizing the Hematoxylin–eosin staining. With the aid of magnetic resonance imaging and signals of high-brightness. We intuitively observed the thickening and edema appeared in the fistula wall, which collectively suggested the formation of a fistula in the perianal area of the rat. Distinguish from the current models of anal fistula modeling including the body surface of fistula, backside of fistula and drainage wire of fistula, our model revealed multifaceted advantages such as quicker generation, higher modeling rate, preferable stability, better consistency, cost-effective, and in particular, more convenient to mimic clinical manifestations of anal fistula. Anal fistula is a refractory and recurrent anorectal disease with a spectrum of complications such as purulent exudates, abscess, granulomatous inflammation, highly exposed fistula and intolerable itching , 2. CurrAs mentioned above, despite the reported methodologies  for constructing disease models by investigators in the field, yet most of the experimental models for more accurately mimicking the symptoms and pathological changes of anal fistula disease are largely obscure. In details, the majority of the current models are difficult to achieve the uniformity epithelialization of fistula and dissimilar from the formation of anal fistula in clinical practice –8.2 aluminum wire to pass the anal sphincter with 1 cm from left or right side of the anus, followed by rotating and fixing rats with a suitable length after penetrating the skin to keep rats hanging around the anal sphincter. Thirdly, the rats were continuously given fresh water with 5% DSS addition for one week to generate the general symptoms of anal fistula including the increased inflammatory response, the red and swollen fistula, tissue fluid exudation, anus with locally moist, and fecal secretions. Fourthly, the pathological changes of anal fistula in rats were evaluated by routine sectioning and hematoxylin and eosin (H and E) staining. As shown by the histopathological examination, typical inflammatory granulation tissues in the fistula wall along with tissue destruction of mucous epithelium were intuitively observed. According to the longitudinal section and cross section of anal fistula, we also noticed substantial inflammatory cell infiltration such as lymphocytes, eosinophils and neutrophils in the mucosal layer of anal fistula, together with the red-stained necrotic tissues in the lacuna . Firstly, we utilized an electric razor to shave the animal's hair and to remove the remaining of hair with a depilatory cream in the operation area after anesthesia administration. Secondly, leave the rats on the operating table in prone position and fix the limbs with tape. Using of the PVC-wrapped 2.5 mmDespite the continuous improvement in the remedies of anal fistula with various complications, yet a certain number of patients still endure the long-lasting torments both physically and mentally due to the deficiency of effective models for disease remodeling. For instance, the surface fistula model or the dorsal fistula model reveals no correlation with anal fistula, while the anal drainage fistula model has inherent defects in the consistency of fistula epithelialization and drainage biomaterials as well as the time-consuming process. Similarly, the anal screw wire fistula model has been reported with a modeling time for over 30 days but with low-efficient infectious corrosion in perianal region and the difficulty in removing the threaded wire.Distinguish from the current animal models of "irrational" anal fistula, our model possessed three prominent advantages. Firstly, it preferably mimicked the symptoms of anal fistula patients with contaminated fistula wounds by feces on the occurrence of diseases in the clinic, which supplied overwhelming new model for dissecting the pathology and therapeutics. In particular, the results of MRI and H&E examinations were highly consistent with the signal intensity and pathological characteristics of anal fistulas. Secondly, this strategy with a higher success rate, a shorter molding cycle, more reliable repeatability, together with minimal surgical risks and cost-effective. In details, our rat anal fistula model was constructed by combining BLV single-core electrolytic aluminum with 5% DSS for one week, and all of the rats revealed typical pathomorphological  and histopathological  characteristics of anal fistula, which were distinguish from the current models with the multifaceted shortcomings as mentioned above. Thirdly, our model was adequate to imitate multiple complications of infectious anal fistula involved in Crohn's disease and ulcerative colitis. Collectively, our methodology would provide a novel "rational" model for further illuminating the pathogenesis and drug development for anal fistula-associated intractable and recurrent disorders in clinical practice in future.