Although symptomatic treatment is widely applied in clinical practice， it is often regarded as a relatively low-level therapeutic method. Based on Traditional Chinese Medicine （TCM） state theory， the macroscopic， mesoscopic， and microscopic characterization parameters of TCM symptomatology are horizontally integrated， the full life cycle of states （pre-disease， incipient disease， manifest disease， post-disease） is vertically covered， and the cognitive system of "symptoms" is reconstructed from multiple dimensions. Accordingly， the application approach of symptomatic treatment at different state stages is proposed： implementing preventive intervention in the pre-disease state， strengthening the interception of disease progression in the incipient disease state， regulating dynamic development and treatment in the manifest disease state， and formulating a staged diagnosis and treatment strategy which focuses on functional rehabilitation in the post-disease state.

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

Abstract The COVID-19 pandemic has posed a series of complex challenges. COVID-19 in children and adolescents is generally less severe than in adults and the elderly; however, some children and adolescents may experience severe complications and adverse health effects even after mild or asymptomatic COVID-19 infections. The article focuses on gathering the epidemic characteristics, health impact, risk factors, prevention and control measures, and vaccination status of children and adolescents with COVID-19 infection to provide recommendations for protecting children and adolescents in the post COVID-19 era.

As a Chinese saying goes， "good Chinese medicinal material makes good medicine"， the quality of Chinese herbal medicines is related to the development prospect of Chinese medicine industry in China. With the rapid development of new technologies such as traceability methods and monitoring instruments， it is imperative to integrate and innovate traditional Chinese herbal medicines with new-generation information technology in view of the quality problems existing in the current production and circulation of Chinese herbal medicines， and it is of great significance for the construction of traceability system to ensure the quality and safety of Chinese herbal medicines and to promote the industry of Chinese herbal medicines to move towards high-quality development. This paper reviews the development history of the traceability system of Chinese herbal medicines in China， takes the influencing factors of the quality of Chinese herbal medicines as the entry point， and proposes that the construction of the traceability system should satisfy the traceability requirements of the characteristics of Chinese herbal medicines and their traditional medication experience. By analyzing the influencing factors of the quality of Chinese herbal medicines， it is pointed out that focusing on the influencing factors to build a traceability system is of great significance for targeting the problematic links at a later stage and exploring the interrelationship between environmental factors and the quality of Chinese herbal medicines. Based on the previous explorations， the author summarizes the system framework， functional modules and practical applications of the traceability system of Chinese herbal medicines， and looks forward to the development of a traceability system with risk early warning function and expert decision-making function in its functional development. Finally， based on the factors affecting the quality of Chinese herbal medicines， the author puts forward several thoughts on construction of the traceability system， and makes an in-depth analysis and puts forward a solution for the current situation that a unified， standardized and universal traceability system has not yet been built， with a view to providing ideas and references for the construction of traceability system of Chinese herbal medicines.

TCM believes that spleen deficiency is the root cause of emotional abnormalities in chronic fatigue syndrome (CFS), and clinical treatment often involves the heart, liver and kidney. TCM therapy has a significant efficacy in CFS emotional abnormalities. It is mostly treated with oral administration of TCM, acupuncture, moxibustion and massage therapy. It may play a therapeutic role by improving oxidative stress and immune inflammation, regulating nerve-endocrine, controlling energy metabolism and other ways. It is suggested to establish the syndrome differentiation standard of CFS emotional abnormality in the future, so as to improve the accuracy of syndrome differentiation and treatment; form a perfect treatment guide or expert consensus to guide the standardized application of various internal and external treatment methods; explore objective indicators based on the pathogenesis, and focus on the morphological and functional changes of disease target brain regions with the help of neuroimaging techniques, so as to improve the diagnosis and prognosis evaluation of CFS; based on the guidance of TCM theory, improve the CFS emotional abnormal animal modeling method.

Objective:Flotillin-2(FLOT2)is a prototypical oncogenic and a potential target for cancer therapy.However,strategies for targeting FLOT2 remain undefined.Post-translational modifications are crucial for regulating protein stability,function,and localization.Understanding the mechanisms and roles of post-translational modifications is key to developing targeted therapies.This study aims to investigate the regulation and function of lysine acetylation of FLOT2 in nasopharyngeal carcinoma,providing new insights for targeting FLOT2 in cancer intervention. Methods:The PhosphoSitePlus database was used to analyze the lysine acetylation sites of FLOT2,and a lysine acetylation site mutation of FLOT2[FLOT2(K211R)]was constructed.Nasopharyngeal carcinoma cells were treated with histone deacetylase(HDAC)inhibitor trichostatin A(TSA)and Sirt family deacetylase inhibitor nicotinamide(NAM).TSA-treated human embryonic kidney(HEK)-293T were transfected with FLOT2 mutant plasmids.Co-immunoprecipitation(Co-IP)was used to detect total acetylation levels of FLOT2 and the effects of specific lysine(K)site mutations on FLOT2 acetylation.Western blotting was used to detect FLOT2/FLAG-FLOT2 protein expression in TSA-treated nasopharyngeal carcinoma cells transfected with FLOT mutant plasmids,and real-time reverse transcription PCR(real-time RT-PCR)was used to detect FLOT2 mRNA expression.Nasopharyngeal carcinoma cells were treated with TSA combined with MG132 or chloroquine(CQ)to analyze FLOT2 protein expression.Cycloheximide(CHX)was used to treat HEK-293T cells transfected with FLAG-FLOT2(WT)or FLAG-FLOT2(K211R)plasmids to assess protein degradation rates.The BioGrid database was used to identify potential interactions between FLOT2 and HDAC6,which were validated by Co-IP.HEK-293T cells were co-transfected with FLAG-FLOT2(WT)/FLAG-FLOT2(K211R)and Vector/HDAC6 plasmids,and grouped into FLAG-FLOT2(WT)+Vector,FLAG-FLOT2(WT)+HDAC6,FLAG-FLOT2(K211R)+Vector,and FLAG-FLOT2(K211R)+HDAC6 to analyze the impact of K211R mutation on total lysine acetylation levels.In 6-0B cells,overexpression of FLOT2(WT)and FLOT2(K211R)was performed,and the biological functions of FLOT2 acetylation site mutants were assessed using cell counting kit-8(CCK-8),colony formation,and Transwell invasion assays. Results:The PhosphoSitePlus database indicated that FLOT2 has an acetylation modification at the K211 site.Co-IP confirmed significant acetylation of FLOT2,with TSA significantly increasing overall FLOT2 acetylation levels,while NAM had no effect.Mutation at the K211 site significantly reduced overall FLOT2 acetylation,unaffected by TSA.TSA decreased FLOT2 protein expression in nasopharyngeal carcinoma cells without affecting FLOT2 mRNA levels or FLOT2(K211R)protein expression in transfected cells.The degradation rate of FLOT2(K211R)protein was significantly slower than that of FLOT2(WT).The proteasome inhibitor MG132 prevented TSA-induced FLOT2 degradation,while the lysosome inhibitor CQ did not.BioGrid data suggested a potential interaction between FLOT2 and HDAC6,confirmed by Co-IP.Knockdown of HDAC6 in nasopharyngeal carcinoma cells significantly increased FLOT2 acetylation;co-transfection of HDAC6 and FLAG-FLOT2(WT)significantly decreased total lysine acetylation levels,whereas co-transfection of HDAC6 and FLAG-FLOT2(K211R)had no effect.Knockdown of HDAC6 significantly reduced FLOT2 protein levels without affecting mRNA levels.MG132 prevented HDAC6-knockdown-induced FLOT2 degradation.Knockdown of HDAC6 significantly accelerated FLOT2 degradation.Nasopharyngeal carcinoma cells transfected with FLOT2(K211R)showed significantly higher proliferation and invasion than those transfected with FLOT2(WT). Conclusion:The K211 site of FLOT2 undergoes acetylation modification,and HDAC6 mediates deacetylation at this site,inhibiting proteasomal degradation of FLOT2 and maintaining its stability and tumor-promoting function in nasopharyngeal carcinoma.

OBJECTIVE Exploring the TNC gene mutations in a family with hereditary hearing loss and their relationship with clinical phenotypes.METHODS Draw the family pedigree chart,analyze the inheritance pattern,and assess the clinical phenotypes of family members using audiologic,imaging,and vestibular function tests.Perform whole exome sequencing on six members of the family to identify candidate mutations potentially related to hearing loss,and validate the distribution of these candidate mutations within the family and in normal controls using Sanger sequencing.RESULTS A heterozygous mutation c.5110G>T(p.Ala1704Ser)in exon 17 of the TNC gene on chromosome 9 was identified in the family.This mutation is associated with hereditary hearing loss.Carriers of this gene mutation all presented with normal hearing at birth and hearing decline during childhood;imaging examinations showed no abnormalities in the middle ear or inner ear structures.CONCLUSION This study reports for the first time the association between the heterozygous mutation c.5110G>T(p.Ala1704Ser)in the TNC gene and hereditary hearing loss,providing new evidence for molecular diagnosis and genetic counseling in cases of hereditary hearing loss.

Standardized patient (SP) has been widely used for medical teaching and assessment in medical colleges at home and abroad. Pediatric consultations are mostly directed toward parents, so in pediatric education, SP is usually referred to as standardized family (Sfam), which is trained to portray the patient's family members. At present, the development of Sfam in pediatric teaching in China is relatively slow. Based on the characteristics of pediatric teaching, the paper summarizes the necessity of Sfam, the application of different types of Sfam, the integration of Sfam with other clinical teaching methods, and the value of Sfam in pediatric teaching, and also discusses the future direction and prospects of Sfam combined with artificial intelligence in pediatric teaching. After years of development, Sfam has been proved to be an effective teaching model. We hope this paper can help more pediatric clinical educators gain a deeper understanding of the Sfam teaching method, and promote the application of Sfam in pediatric teaching to maximize its role in advancing the development of pediatric education.

Breast cancer has been the second most common solid tumor that metastasizes to the central nervous system after lung cancer.Triple-negative breast cancer(TNBC)has an earlier occurrence and high incidence of brain metastasis with its associated poor prognosis and limited treatment options due to the presence of the blood-brain barrier and lack of targeted drugs.Local treatment,including surgery and radiation therapy,are still the main therapy for brain metastasis.Surgical resection can not only relieve neurologic impairment of brain metastasis patients,but also can clarify the pathological type.Moreover,surgical resection combined with radiotherapy can improve the prognosis of brain metastasis patients compared to surgery or radiotherapy alone.By now,whole-brain radiation therapy(WBRT)is still considered the gold standard for multiple brain metastases,and meningeal metastases,but it will lead to neurocognitive decline,so hippocampal avoidance is essential.For selected patients with oligometastases,stereotactic radiotherapy has replaced WBRT to reduce cognitive toxicity.However,local treatment of TNBC brain metastasis cannot control the progress of brain metastasis and has significant side effects,so systemic therapy is needed.Chemotherapy drugs such as capecitabine and cisplatin can penetrate the blood-brain barrier,but their efficacy is limited.Therefore,the research and development of new targeted drugs and the exploration of new targets are necessary for TNBC brain metastasis.Research has found that patients carrying germline BRCA1/2 mutations have a higher risk of brain metastasis.Currently,the poly adenosine diphosphate ribose polymerase(PARP)inhibitor demonstrated antitumor activity in patients with advanced breast cancer and a germline BRCA1/2 mutation,and it can penetrate the blood-brain barrier.The phase Ⅲ trial EMBRACA reported that the PARP inhibitor talazoparib can prolong the progression-free survival of TNBC patients with brain metastasis.In addition,antibody drug conjugates(ADCs)trastuzumab deruxtecan(T-DXd)can also penetrate the blood-brain barrier.Studies such as DEBBRAH have shown that T-DXd has significant therapeutic effects in HER2 positive brain metastasis patients,while research on HER2 low expression patients has not yet reached the endpoint,and its role in TNBC brain metastasis is worth looking forward to.Sacituzumab govitecan(SG)is also an ADC composed of an antibody targeting the human trophoblast cell-surface antigen 2.The phase Ⅲ ASCENT study showed that in the full population(including 61 patients with brain metastasis),SG could significantly prolong the progression-free survival of advanced TNBC patients compared to the patients who received chemotherapy.ANG1005,a novel taxane derivative,can cross the blood-brain barrier as well.A multicenter,open-label phase Ⅱ study revealed that ANG1005 could prolong overall survival of patients with brain metastasis.In addition,phosphoinositide3-kinase,(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)pathway inhibitors,fatty acid synthase inhibitors,and the drugs with new delivery systems have become potential treatment options for TNBC brain metastasis patients.Although the Impassion 130 reported that no benefit trend for immunotherapy in TNBC brain metastasis,basic research has shown that radiotherapy combined with immunotherapy has a synergistic effect.Currently,multiple clinical trials(NCT03483012,NCT03449238,etc.)are exploring the efficacy of radiotherapy combined with immunotherapy in brain metastasis,and the results are promising.This article reviewed the research progress of TNBC brain metastasis treatment.

The histopathological growth patterns (HGPs) of colorectal cancer (CRC) liver metastasis reflect the complicated and varied interactions between tumor cells and host microenvironment. Exploring the tumor vascular and immunological features of HGPs, the relationship between HGPs and anti-tumor treatment efficacy, and HGPs prediction methods may have potential clinical aplication value for making optimal treatment strategies, evaluating patients' prognosis, and monitoring disease progression.