ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

AIM: To explore the current status, research hotspots, and trends of global uveitis research to provide a theoretical basis and references for researchers in the field of uveitis, and promote further development in this area.METHODS: Relevant literatures on uveitis were retrieved from the China National Knowledge Infrastructure(CNKI)database, Wanfang database, and Web of Science core collection database since their establishment until 24 August 2023. The country/publishing institutions, research authors, high-frequency keywords, and burst keywords were visual analyzed by using software such as GraphPad Prism 9, CiteSpace 6.2. R2, and VOSviewer.RESULTS: Research teams for uveitis have been formed in various countries globally. The top three countries in terms of publications are the United States of America(7 585 papers), the United Kingdom(2 412 papers)and Germany(1 679 papers). The top three foreign institutions in terms of publications are Harvard University, Oregon Health & Science University, and Moorfields Eye Hospital, while the top three domestic institutions are Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Chongqing Medical University, and Zhongshan Ophthalmic Center, Sun Yat-sen University. The analysis of high-frequency keywords and burst keywords in Chinese and English shows that research hotspots mainly focus on exploring pathogenesis and different treatment methods for uveitis. The research hotspots related to uveitis treatment are transitioning to molecular biology-related research topics, such as molecular biological signaling pathways(NF-κB signaling pathway with a strength value of 22.89), biological agents(adalimumab with a strength value of 32.21), and tumor necrosis factor(with a strength value of 48.44). Related research is also expanding to basic experiments on relevant rats.CONCLUSIONS: In recent years, the research hotspots and trends of global uveitis mainly focus on precise diagnosis, pathogenesis, and more effective treatment methods. It is important for more scholars to dedicate themselves to uveitis-related research in the future to make breakthroughs and progress in the field. More large-scale and multicenter clinical studies on uveitis can provide high-quality research evidence.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for circular superficial esophageal cancer.Methods:A retrospective analysis was conducted on 74 consecutive cases of circular superficial esophageal squamous cell carcinoma treated with ESD at Nanjing Drum Tower Hospital from January 2015 to December 2019. The success rate of ESD, curative resection rate, incidence of complications, and additional treatment were mainly observed.Results:One case was transferred to surgery, and the remaining 73 cases successfully completed ESD treatment. The success rate of ESD was 98.6%. Postoperative pathology of ESD revealed that 39 cases achieved curative resection, with a curative resection rate of 53.4% (39/73). Intraoperative muscle layer injury occurred in 15 cases (20.5%), and intraoperative perforation occurred in 1 case (1.4%). Two cases (2.7%) experienced delayed bleeding, and one case (1.4%) experienced delayed perforation. Eleven cases were lost to follow-up, and the remaining 62 cases received follow-up for 36.4±19.0 months. Among the follow-up cases, 12 underwent additional surgery and 5 cases additional chemotherapy and radiotherapy. Among the 57 patients with follow-up data who did not underwent surgery, 49 developed esophageal stenosis after ESD, with an incidence rate of 86.0%.Conclusion:ESD for circular superficial esophageal cancer is generally safe, but it is prone to muscle layer injury during the operation, with a low curative resection rate, a high incidence of postoperative esophageal stenosis, and a high proportion of additional surgical procedures.

Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

Objective To evaluate the methylation levels of DNA at six specific CpG sites located in the mRNA region of histone cluster 4 subfamily F member 6(HIST1H4F)gene and determine their diagnostic signifi-cance about lung cancer.Methods The DNA methylation levels of 15 cases of lung cancer and adjacent paired nor-mal lung tissue were detected using pyrophosphate sequencing.Based on preliminary evaluation,a methylation-sensitive restriction enzyme-fluorescence quantitative PCR(MSRE-qPCR)method was developed to detect DNA methylation levels in the test group(60 cases of lung adenocarcinoma,38 cases of squamous cell carcinoma,30 cases of benign diseases,and 26 cases of normal lung tissue)and the validation group(36 cases of lung adenocarci-noma,16 cases of squamous cell carcinoma,21 cases of benign diseases,and 23 cases of normal lung tissue).The diagnostic value was evaluated using ROC curves.Results The results of pyrophosphate sequencing showed that the methylation levels of lung cancer were significantly higher than that of paired normal lung tissue(P<0.005).The detection results of MSRE-qPCR showed that the areas under the ROC curve for diagnosing lung cancer in the test group and validation group were 0.894 and 0.888,with sensitivity of 76.5%and 73.1%,and specificity of 92.9%and 97.7%,respectively.The methylation levels were significantly positively correlated with smoking in lung cancer patients(r=0.273,P<0.01).Conclusion The six CpG sites in the mRNA region of the HIST1H4F gene can serve as biomarkers for diagnosing lung cancer,providinga new molecular target for clinical lung cancer diagnosis.

Objective To compare the difference and consistency between OPD-Scan Ⅲ and IOL-Master 700 in the measurement of corneal curvature(flat keratometry,K1 and steep keratometry,K2)and horizontal corneal diameter(white-to-white(WTW)distance).Methods Totally 268 patients with 328 eyes(164 right eyes and 164 left eyes)who underwent cataract surgery at the Department of Ophthalmology of the Aerospace Centre Hospital from October 2021 to September 2022 were selected for this study.The K1,K2,and WTW values of the sampled right or left eyes were measured and analyzed using OPD-Scan Ⅲ and IOL-Master 700,respectively.Parameter comparisons were performed through paired t-tests;correlations between parameters were detected through the Pearson correlation analysis;and the Bland-Altman method and intragroup correlation coefficient(ICC)analysis were employed to determine the consistency of parameter measurements between the two instruments.Results The K1 and K2 values measured by OPD-Scan Ⅲ were greater than those measured by IOL-Master 700,while the WTW values were lower than those measured by IOL-Master 700,but the differences were statistically significant(all P＜0.001).K1,K2,and WTW values measured by OPD-Scan Ⅲ were positive-ly correlated with the corresponding values measured by IOL-Master 700,and the differences were statistically significant(all P＜0.001).The proportions of K1,K2,and WTW values outside the 95％limits of agreement for both instruments were within 5％,but the absolute value of the difference in values within the 95％limits of agreement was close to or more than(1.0)D,indicating a sizeable clinical deviation.ICC analysis confirmed a good consistency between K1 and K2 values of the left and right eyes measured by the two instruments(ICC＞0.90).The difference in WTW values measured by the two instruments was significantly correlated with K2 values(both P＜0.05).There were 5 samples(83.33％)outside the positive deviation range of WTW values,of which K2 measured by IOL-Master 700 was above 47.03.Conclusion The OPD-Scan Ⅲ and IOL-Master 700 have been found to have measurement biases when assessing K1,K2 and WTW.In clini-cal practice,the two instruments cannot be interchanged as an alternative to each other.The WTW values measured by IOL-Master 700 are greater than those obtained by OPD-Scan Ⅲ;when K2≥47.03,the WTW values may not be reliably ref-errable.