arcopenia is a systemic skeletal muscle disorder characterized by a decrease in skeletal muscle mass and progressive decline in function， with multiple signaling pathways involved in its occurrence and development. Among them， the AMP-activated protein kinase （AMPK） signaling pathway， as a key pathway regulating cellular energy homeostasis， plays an important role in the regulation of skeletal muscle metabolism and functional maintenance by improving abnormalities in glucose and lipid metabolism， balancing skeletal muscle protein synthesis and degradation， improving mitochondrial function， promoting autophagy， and inhibiting inflammatory responses and oxidative stress. This article reviews the research progress on how various traditional Chinese medicine （TCM） monomers， including polyphenols， flavonoids， and terpenoids； various traditional Chinese medicine extracts， such as those from Lycium barbarum ， Asini Corii Colla， and Panax quinquefolium ， and TCM compounds， such as Guiqi zhuangjin decoction， Jianpi qiangji granules， and Qigu capsules， intervene in sarcopenia by regulating the AMPK signaling pathway to promote muscle protein synthesis， inhibit protein degradation， improve mitochondrial function， and alleviate inflammation and oxidative stress. Additionally， their molecular mechanisms are explored. The aim is to deeply elucidate the basis of TCM in the prevention and treatment of sarcopenia and to provide theoretical support for the development of related innovative drugs.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

It is believed that diabetes complicated with coronary heart disease is closely related to the functional interplay of the heart， spleen， and kidneys. This paper proposed the concept of the heart-spleen-kidney as a unified system for understanding and treating the disease. At the early stage， spleen and kidney deficiency leads to the internal accumulation of phlegm， dampness， and turbid lipids， causing impaired blood circulation and vascular obstruction， so treatment should focus on tonify the kidneys and strengthening the spleen， activating blood circulation and resolving stasis， using the self-prescribed Tangxin Maiwen Formula （糖心脉温方）. As the disease progresses， further decline of spleen and kidney function results in inadequate nourishment of the heart， leading to blood stasis and the accumulation of phlegm， dampness， and turbid lipids， which may transform into pathogenic heat and toxins， causing heart damage， then treatment should emphasize on boosting qi and nourishing yin， clearing heat， activating blood and resolving toxins， using the self-prescribed Tangxin Maiqing Formula （糖心脉清方）. In advanced stages， three zang organs， the heart， spleen， and kidneys， become severely impaired， leading to mental activity fail to be nourished and abnormal cognitive functions， so treatment should focus on harmonizing the three zang organs simultaneously， using the self-prescribed Yunpi Tiaoxin Decoction （运脾调心汤）. This approach aims to provide a clinical framework for the diagnosis and treatment of diabetes with coronary heart disease.

This article summarized clinical experience in differentiating and treating non-obstructive hypertrophic cardiomyopathy （HCM） based on the concept of nourishing the heart and softening the hardness. It is considered that HCM belongs to the category of "heart accumulation"， with the fundamental cause being depletion of the spleen and kidney， and phlegm-stasis accumulation， as well as qi-yin exhaustion， serving as the manifestations. Spleen and kidney depletion leads to the transformation of phlegm and stasis， which accumulate in the heart； over time， this phlegm-stasis accumulation consumes heart qi and yin， resulting in the heart being deprived of nourishment， which eventually leads to the damage to both the function and structure of heart. Therefore， the method of nourishing the heart and softening the hardness is proposed for the treatment of non-obstructive HCM. Emphasis is placed on softening hardness and dissipating masses throughout the entire treatment process， often using Modified Siwei Ruanjian Formula （四味软坚方加减）. During periods with prominent symptoms， the main treatment is boosting qi and nourishing yin to soften hardness and dissipate masses with self-made Yuxin Ruanjian Formula （自拟育心软坚方） in modifications； in stable periods， the main treatment is boosting kidney and fortifying spleen to soften hardness and dissipate masses with self-made Pishen Tongzhi Formula （脾肾同治方） in modifications.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

Heat shock factor 1(HSF1)is a core transcription factor in cellular stress response and protein homeostasis maintenance,and is widely involved in biological processes such as cell growth,differentiation,and metabolism.This study aims to design antigenic peptides of the sheep HSF1 protein and prepare polyclonal antibodies through bioinformatics analysis and immunologi-cal techniques,and verify their application effects in sheep lung and testis tissues.Firstly,the se-quence,structure,and evolution of the sheep HSF1 gene were analyzed using bioinformatics meth-ods,and key antigenic epitopes were predicted.Then,suitable peptide fragments were selected for synthesis,emulsified with Freund's complete adjuvant or incomplete adjuvant,and used to immu-nize New Zealand rabbits.The specificity and effectiveness of the antibodies were verified by indi-rect ELISA,Western blot,and immunohistochemistry(IHC)experiments.The results showed that the HSF1 protein is 564 amino acids(aa)in length,with a molecular weight of 60.76 kDa,a theo-retical isoelectric point(pI)of 5.32,and is hydrophilic and unstable.Phylogenetic tree analysis revealed that HSF1 is highly conserved among most members of the Bovidae family,as well as in humans,mice,rats,and other species,but with local site differences.Sheep HSF1 is most closely related to goat HSF1,followed by Canadian bighorn sheep and goral.The phosphorylation sites of sheep HSF1 are predominantly concentrated in the middle and C-terminal regions,which is largely consistent with the predicted results for human HSF1,though some local differences exist.The prepared polyclonal antibodies exhibited a titer of over 1:8000 in recognizing the sheep HSF1 pro-tein,and Western blot experiments confirmed clear bands with consistent molecular weight,indica-ting high specificity of the antibodies.Furthermore,the expression and specific distribution of HSF1 were detected in sheep lung and testis tissues.This study successfully prepared polyclonal antibodies based on the sheep HSF1 antigen peptide and,for the first time,detected the immuno-histochemical distribution of HSF1 in the testis and lung tissues of Argali hybrid sheep.This pro-vides an important tool for further exploring the physiological role of HSF1 in Argali hybrid sheep and its potential applications in stress response,disease prevention,and treatment.

Heat shock factor 1(HSF1)is a core transcription factor in cellular stress response and protein homeostasis maintenance,and is widely involved in biological processes such as cell growth,differentiation,and metabolism.This study aims to design antigenic peptides of the sheep HSF1 protein and prepare polyclonal antibodies through bioinformatics analysis and immunologi-cal techniques,and verify their application effects in sheep lung and testis tissues.Firstly,the se-quence,structure,and evolution of the sheep HSF1 gene were analyzed using bioinformatics meth-ods,and key antigenic epitopes were predicted.Then,suitable peptide fragments were selected for synthesis,emulsified with Freund's complete adjuvant or incomplete adjuvant,and used to immu-nize New Zealand rabbits.The specificity and effectiveness of the antibodies were verified by indi-rect ELISA,Western blot,and immunohistochemistry(IHC)experiments.The results showed that the HSF1 protein is 564 amino acids(aa)in length,with a molecular weight of 60.76 kDa,a theo-retical isoelectric point(pI)of 5.32,and is hydrophilic and unstable.Phylogenetic tree analysis revealed that HSF1 is highly conserved among most members of the Bovidae family,as well as in humans,mice,rats,and other species,but with local site differences.Sheep HSF1 is most closely related to goat HSF1,followed by Canadian bighorn sheep and goral.The phosphorylation sites of sheep HSF1 are predominantly concentrated in the middle and C-terminal regions,which is largely consistent with the predicted results for human HSF1,though some local differences exist.The prepared polyclonal antibodies exhibited a titer of over 1:8000 in recognizing the sheep HSF1 pro-tein,and Western blot experiments confirmed clear bands with consistent molecular weight,indica-ting high specificity of the antibodies.Furthermore,the expression and specific distribution of HSF1 were detected in sheep lung and testis tissues.This study successfully prepared polyclonal antibodies based on the sheep HSF1 antigen peptide and,for the first time,detected the immuno-histochemical distribution of HSF1 in the testis and lung tissues of Argali hybrid sheep.This pro-vides an important tool for further exploring the physiological role of HSF1 in Argali hybrid sheep and its potential applications in stress response,disease prevention,and treatment.

Objective:To develop a clinical automated diagnostic system for temporomandibular disor-ders(TMD)based on the diagnostic criteria for TMD(DC/TMD)to assist dentists in making rapid and accurate clinical diagnosis of TMD.Methods:Clinical and imaging data of 354 patients,who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024,were retrospectively collected.The study developed a clinical automated diagnostic system for TMD using the DC/TMD,built on the.NET Framework platform with branching statements as its in-ternal structure.Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored.Diagnostic efficacy of the TMD clinical automated diagnostic system for de-generative joint diseases,disc displacement with reduction,disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evalua-ted and compared with a specialist in the field of TMD.Accuracy,precision,specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist.Results:Diagnoses for various TMD subtypes,including pain-related TMD(arthralgia,myalgia,headache attribu-ted to TMD)and intra-articular TMD(disc displacement with reduction,disc displacement with reduc-tion with intermittent locking,disc displacement without reduction with limited opening,disc displace-ment without reduction without limited opening,degenerative joint disease and subluxation),using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD spe-cialist based on DC/TMD.Both the system and the expert showed low sensitivity for diagnosing degenera-tive joint disease(0.24 and 0.37,respectively),but high specificity(0.96).Both methods achieved high accuracy(＞0.9)for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening.The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system,lower than the expert(0.87),while both had high specificity(0.92).The Kappa values for most TMD subtypes were close to 1,ex-cept the disc displacement without reduction without limited mouth opening,which had a Kappa value of 0.68.Conclusion:This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD.The system is designed to facilitate the rapid and accurate diagnosis and classi-fication of TMD,and is expected to be an important tool in clinical scenarios.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.