BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

ObjectiveThis paper proposes a novel real-time bedside pulmonary ventilation monitoring method for the diagnosis of chronic obstructive pulmonary disease (COPD), based on electrical impedance tomography (EIT). Four indicators—center of ventilation (CoV), global inhomogeneity index (GI), regional ventilation delay inhomogeneity (RVDI), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC)—are calculated to enable the spatiotemporal assessment of COPD. MethodsA simulation of the respiratory cycles of COPD patients was first conducted, revealing significant differences in certain indicators compared to healthy individuals. The effectiveness of these indicators was then validated through experiments. A total of 93 subjects underwent multiple pulmonary function tests (PFTs) alongside simultaneous EIT measurements. Ventilation heterogeneity under different breathing patterns—including forced exhalation, forced inhalation, and quiet tidal breathing—was compared. EIT images and related indicators were analyzed to distinguish healthy individuals across different age groups from COPD patients. ResultsSimulation results demonstrated significant differences in CoV, GI, FEV₁/FVC, and RVDI between COPD patients and healthy individuals. Experimental findings indicated that, in terms of spatial heterogeneity, the GI values of COPD patients were significantly higher than those of the other two groups, while no significant differences were observed among healthy individuals. Regarding temporal heterogeneity, COPD patients exhibited significantly higher RVDI values than the other groups during both quiet breathing and forced inhalation. Moreover, during forced exhalation, the distribution of FEV₁/FVC values further highlighted the temporal delay heterogeneity of regional lung function in COPD patients, distinguishing them from healthy individuals of various ages. ConclusionEIT technology effectively reveals the spatiotemporal heterogeneity of regional lung function, which holds great promise for the diagnosis and management of COPD.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

ObjectiveFat infiltration has been shown to be closely related to muscle mass loss and a variety of muscle diseases. This study proposes a method based on phase-angle electrical impedance tomography (ΦEIT) to visualize the electrical characteristic response caused by muscle fat infiltration, aiming to provide a new technical means for early non-invasive detection of muscle mass deterioration. MethodsThis study was divided into two parts. First, a laboratory pork model was constructed to simulate different degrees of fat infiltration by injecting1 ml or 2 ml of emulsified fat solution into different muscle compartments, and the phase angle images were reconstructed using ΦEIT. Second, a human experiment was conducted to recruit healthy subjects (n=8) from two age groups (20-25 years old and 26-30 years old). The fat content percentage η_fat of the left and right legs was measured by bioelectrical impedance analysis (BIA), and the phase angle images of the left and right calves were reconstructed using ΦEIT. The relationship between the global average phase angle Φ_M and the spatial average phase angle Φ_Mi of each muscle compartment and fat infiltration was further analyzed. ResultsIn the laboratory pork model, the grayscale value of the image increased with the increase of η_fat and Φ_M showed a downward trend. The results of human experiments showed that at the same fat content percentage, the Φ_M of the 26-30-year-old group was about 20%-35% lower than that of the 20-25-year-old group. The fat content percentage was significantly negatively correlated with Φ_M. In addition, the M₂ (soleus) compartment was most sensitive to fat infiltration, and the spatial average phase angles of the M₂ (soleus), M₃ (tibialis posterior and flexor digitorum longus), and M₄ (tibialis anterior, extensor digitorum longus, and peroneus longus) compartments all showed significant inter-group differences. ConclusionΦEIT imaging can effectively distinguish different degrees of fat infiltration, especially in deep, small or specially located muscles, showing high sensitivity, demonstrating the potential application of this method in local muscle mass monitoring and early non-invasive diagnosis.

Objective:To quantify the diagnostic index of probe-based confocal laser endomicroscopy (pCLE) for diagnosing Helicobacter pylori ( HP)-associated chronic atrophic gastritis (HpCAG), and to evaluate the efficacy of the quantified diagnostic index for HpCAG. Methods:The study was divided into two stages. The first stage prospectively included patients undergoing gastroscopy, endoscopic biopsy and 13C breath test from November 2021 to September 2022 at the Second Affiliated Hospital of Baotou Medical College. The capillary diameter (CD), cells spacing (CS), gland spacing (GS), and gland area (GA) in the pCLE field of offline video was measured with Image J. The diagnostic criteria of HpCAG by quantitative indicators under pCLE was established by analyzing the area under the receiver operating characteristic (ROC) curve (AUC). In the second stage, the cases with pCLE examination and 13C breath test at the Second Affiliated Hospital of Baotou Medical College from October 2021 to October 2022 were included. The cases that overlapped with the first stage were excluded. The trial was single-blind, with endoscopists and pathologists blind to each other's diagnoses. The diagnosis of pCLE was conducted according to the criteria obtained in the first stage, and the consistency between pCLE diagnosis and the results of histopathology and 13C breath test was analyzed. Results:The first stage enrolled 191 specimens from 35 patients. According to the pathological results of endoscopic biopsy and 13C breath test results, patients and gastric mucosa samples were divided into 4 groups, HP-positive CAG group ( n=59), HP-positive non-CAG group ( n=52), HP-negative CAG group ( n=40), and HP-negative non-CAG group ( n=40). ROC curve analysis results showed that in HP-positive patients, the optimal critical value of GS to distinguish between CAG and non-CAG gastric mucosa was 29.68 μm, and the AUC was the largest among the 4 parameters. In HP-negative patients, the optimal critical value of GS for distinguishing gastric mucosa from CAG and non-CAG was 23.57 μm, and the AUC was the largest among the 4 parameters. In patients with non-CAG, the optimal critical value for GS to distinguish HP-positive and HP-negative gastric mucosa was 20.57 μm, and the AUC was the largest among the 4 parameters. In patients with CAG, the optimal critical values of CD, CS, GS and GA to distinguish between HP-positive and HP-negative gastric mucosa were 13.23 μm, 1.38 μm, 34.03 μm and 6 066.5 μm 2, respectively, and the AUC were 0.608, 0.888, 0.849 and 0.900, respectively. Finally, GS was selected to distinguish between HpCAG and non-HpCAG gastric mucosa, and the optimal critical value was 31.71 μm. However, considering that it was difficult to measure the distance of 31.71 μm by the ruler below the image, the critical value was changed to 30 μm, so GS>30 μm was used as the diagnostic criteria for HpCAG in pCLE, and the diagnostic sensitivity and the specificity were 91.5% and 76.0%, respectively. In the second phase 224 specimens from 80 patients were observed. The sensitivity, the specificity, the positive predictive value, the negative predictive value and accuracy of pCLE (GS>30 μm) in the diagnosis of HpCAG were 96.5% (164/170), 88.9% (48/54), 96.5% (164/170), 88.9% (48/54) and 94.6% (212/224), respectively, with excellent diagnostic agreement with histopathology and 13C breath test (Kappa=0.854). Conclusion:The quantitative monitoring of gastric mucosal microstructure can be achieved under pCLE, and the quantifying indicators are helpful to improve the accuracy of HpCAG diagnosis.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Previous research on traditional Chinese medicine tongue inspection has mainly focused on its development,clinical application,and objectification,ignoring the fundamental question of "why tongue inspection is important in traditional Chinese medicine diagnosis" and neglecting the dominant role of traditional Chinese medicine brain thinking activities during diagnosis. Therefore,applying modern cognitive neuroscience technology to explore the impact of tongue inspection information on traditional Chinese medicine diagnostic thinking from an empirical research perspective may open up a new path for future tongue inspection research. This article proposes the combined application of eye tracking and event-related potential technology,drawing on the experimental paradigm of text reading inference correction in cognitive psychology,to collect eye movement and electroencephalogram data of participants induced by changes in tongue information during the reading process of traditional Chinese medicine medical records. This method can achieve synchronous observation of the focus areas and electroencephalogram signals of the subjects during the reading process,and provide cognitive scientific evidence for "why tongue inspection is important in traditional Chinese medicine diagnosis" through statistical data analysis. This research approach integrates the theories,techniques,and methods of traditional Chinese medicine and cognitive science,and is of great significance for developing cognitive thinking research in traditional Chinese medicine.

Objective:To summarize the clinical features of 14 cases with clinically and genetically diagnosed progressive pseudorheumatoid dysplasia(PPRD) and analyze the characteristics of joint lesions caused by PPRD to provide references for clinical diagnosis and treatment of PPRD.Methods:A retrospective analysis was made on the clinical data and genetic test data of 14 patients admitted to Children′s Hospital, Capital Institute of Pediatrics and cooperative units, from December 2017 to September 2023.An observational retrospective analysis was performed on hospitalization and follow-up data, and correlation factors were analyzed using the Kendall correlation test.Results:The 14 patients, including 6 males and 8 females, were all Chinese Han children.The average age of onset was 6.12 years(2-11 years), the average age of diagnosis was 10.61 years old(5-17 years old), and the average duration of the disease was 4.46 years(0.5-6.0 years) at diagnosis.The number of joint involvements ranged from 4 to 14, with an average of 9.20.There were 12 patients with claudication as the first symptom.All these 14 children had limited hip mobility and no obvious hip pain.The hip joint imaging indicated that space narrowing occurred in 11 cases, femoral neck shortening in 2 cases, femoral head displacement in 4 cases, and articular surface sclerosis, cystic degeneration or bone destruction in 8 cases.The joints of the four limbs were mainly manifested as enlargement of the proximal interphalangeal joints and metacarpophalangeal joints of both hands.The other joints were knees(11 cases), elbows(8 cases), wrists(7 cases) and ankles(5 cases) in the order of easy involvement, and the shoulder joint was less involved(1 case).The spine was mainly characterized by changes in the curvature, and limited movement was found in 8 cases.Thoracic and lumbar spines were mainly involved(13 cases), while cervical involvement was rare(1 case).The duration of the disease at diagnosis was positively correlated with the number of joint involvements and the number of joint mobility limitations( r=0.584, 0.671; P=0.007, 0.002).In this study, 8 children were misdiagnosed as juvenile idiopathic arthritis, and the longest misdiagnosis time was 6 years.All the 14 children had CCN6 gene mutations, including 10 complex heterozygous mutations and 4 homozygous mutations.Five children had c. 342T>G and c. 667T>G, 4 children had c. 589 + 2(IVS4)T>C, 3 children had c. 866dup, and 2 children had c. 136C>T and c. 624dupA. Conclusions:PPRD is characterized by multiple joint involvements, among which hip involvement is the most common.The lesions are serious and easily misdiagnosed as juvenile idiopathic arthritis.The number of affected joints increases gradually with the prolongation of the disease course.

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.