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

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.

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.

In the context of the complex and ever-changing spectrum of diseases, the traditional Chinese medicine compatibility of prescription and drugs is no longer able to fully meet the needs of clinical diagnosis and treatment. Therefore, this article is based on the diagnosis and treatment model of the combination of disease, syndrome, and symptom, combined with the development achievements of Western medicine, and explores the principles of formulating traditional prescriptions based on the combination of chief, deputy, assistant, and envoy. This article proposes a formulation principle of composing prescriptions with the diagnosis of syndrome as the chief, the diagnosis of disease as the deputy, the treatment of symptoms as the assistant, and the harmonization of medicine as the envoy. This forms a treatment plan with the core link of syndrome differentiation and treatment, disease differentiation and treatment, symptomatic treatment, detoxification, and efficacy enhancement. The purpose of this article is to address the current clinical challenges such as an increasing disease spectrum and the complexity of syndrome patterns and symptom clusters. It aims to provide new insights into traditional Chinese medicine clinical treatment plans and herbal formulation strategies, with the ultimate goal of improving the clinical effectiveness of traditional Chinese medicine.

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.

Objective:To study the epidemic characteristics of human brucellosis in Yunnan Province, and to provide a reliable scientific basis for formulating accurate prevention and control strategies of brucellosis.Methods:The epidemic data of human brucellosis in Yunnan Province from January 2019 to December 2021 were collected from the information system of the China Center for Disease Control and Prevention, as well as annual monitoring data on brucellosis reported by various states (municipalities) in Yunnan Province. Descriptive epidemiological methods were adopted to analyze the epidemic situation, distribution characteristics (time, region, population), and serological and pathogenic monitoring results of brucellosis.Results:From 2019 to 2021, 1 408 cases of brucellosis were reported in Yunnan Province, with an average annual incidence of 1.00/100 000. The number of cases increased from 321 in 2019 to 701 in 2021, and the incidence increased from 0.68/100 000 in 2019 to 1.50/100 000 in 2021. The onset time was mainly from April to September (857 cases). The top 3 regions with the highest number of reported cases were Kunming City (483 cases), Qujing City (379 cases), and Honghe Hani and Yi Autonomous Prefecture (281 cases), accounting for 81.18% (1 143/1 408) of the total number of cases. The age of onset was mainly 20 - < 70 years old, accounting for 89.70% (1 263/1 408). There were 958 males and 450 females, with a sex ratio of 2.13 ∶ 1.00. Farmers were the main occupation, accounting for 84.02% (1 183/1 408). From 2019 to 2021, a total of 26 280 serum samples from key populations of brucellosis were monitored in Yunnan Province, with 572 positive serological tests and a positive rate of 2.18% (572/26 280). A total of 169 strains of Brucella were isolated from blood samples from hospitals throughout the province, including 155 strains of sheep type 3 and 14 strains of sheep type 1. Conclusions:From 2019 to 2021, the incidence of human brucellosis in Yunnan Province has been on the rise, with a high incidence in summer and autumn. The main population affected is young and middle-aged male farmers. Therefore, it is necessary to strengthen disease monitoring and health education for key populations during the high incidence season.

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.

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.