Heterotopic ossification is an important pathological link leading to disability in ankylosing spondylitis （AS）. Imbalance of bone immune microenvironment is the initiating factor for heterotopic ossification in AS， while abnormal osteogenic potential of bone marrow mesenchymal stem cells （BMSCs） is the core link. From the perspective of "bone sweat pore-kidney visceral manifestation" in traditional Chinese medicine， it is believed that dysfunction of "kidney visceral manifestation" is the basis for the induction of heterotopic ossification by bone immune microenvironment and BMSCs， and "bone sweat pore" is their important setting. Accordingly， it is proposed that the kidney and sweat pore should be nourished and regulated to reshape the bone immune microenvironment and BMSCs function， and that obstruction should be removed and the marrow should be unblocked to eliminate the pathological factors that lead to AS heterotopic ossification. This provides a new perspective and basis for the treatment of AS with traditional Chinese medicine.

Stasis-heat is a pathological factor associated with numerous exogenous and internal injuries, representing a pivotal mechanism in disease progression. Its primary cause is fire-heat toxicity. Based on the theory of qi and the holistic perspective of traditional Chinese medicine, this concept emphasizes that the biochemistry of all natural phenomena relies on the dynamic movement of qi ascending, descending, exiting, and entering. Within six qi, "fire" includes sovereign and ministerial fires. While physiological ministerial fire is the source power of life, pathological ministerial fire manifests as violent, intense energy that readily interacts with blood, leading to the formation of stasis-heat. Therefore, this article examines the formation and treatment of stasis-heat resulting from ministerial fire dysfunction. From the perspectives of ministerial fire gasification, the shape and quality of meridians, and the elevation of ministerial fire, it elucidates why the "pericardium-sanjiao-gallbladder" axis is regarded as pivotal. Furthermore, when the "pericardium-sanjiao-gallbladder" ministerial fire axis is unfavorable, and the stagnation of ministerial fire elevation and blockage is crucial to stasis-heat formation. Additionally, the depletion of essence and blood in the liver and kidneys, preventing the proper storage of ministerial fire, forms the pathological foundation. Drawing upon The Inner Canon of Yellow Emperor, this article explores therapeutic principles based on the rules of odor treatment: "when fires in the interior, the treatment of salty and cold, accompanied by bitter and pungent, acid to astringe, bitter to disperse." These principles are applied to achieve specific therapeutic goals: tempering the excess of ministerial fire to cool the nutritive level and transform stasis; adjusting the imbalance of elevation and depression to vent heat and unblock stasis; and restoring the misplaced fire by nourishing blood to expel stasis. Through these approaches, the article aims to reestablish the proper circulation of ministerial fire, dissipate blood stasis, and ultimately eliminate stasis-heat, thereby offering an integrated perspective on its pathogenesis and treatment.

Height， as one of the crucial indicators for assessing children’s growth and development， has consistently been a global focus. With economic development and improvements in social living standards， the clinical management needs for children with short stature have been increasingly growing. While growth hormone brings hope to children with short stature， it also triggers ethical challenges such as medical standardization， expansion of indications， equitable accessibility， and informed consent. To avoid the ethical issues related to the use of pediatric growth hormone， multidimensional and comprehensive clinical management should be implemented for children with short stature， including strictly adhering to medical standards and ethical guidelines， enhancing public awareness， and promoting the standardized development of recombinant human growth hormone （rhGH） therapy and ethics.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

ObjectiveTo analyze the relationship between somatic symptoms， five-state personality and emotional symptoms of bipolar disorder （BD）， and to provide a reference for the clinical diagnosis and treatment of BD. MethodsThe basic information of the BD patients was collected， and the self-administered somatic symptom questionnaire was used to investigate the somatic symptoms with a frequency of ＞20%， which were scored as the somatic symptom scores； the 24-item Hamilton Depression Scale （HAMD） was used to evaluate the patients' depressive symptoms， the Young Mania Rating Scale （YMRS） was used to evaluate the patients' manic symptoms， the Hamilton Anxiety Scale （HAMA） was used to evaluate the patients' anxiety symptoms， and Five-State Personality Test was used to evaluate the patients' five-state personality （including taiyang personality， shaoyang personality， yin-yang balance personality， shaoyin personality， and taiyin personality）. Network analysis and linear regression were used to analyse the correlation between the somatic symptom scores and the five-state personality scores， HAMD scores， YMRS scores， and HAMA scores. ResultsThere were 269 patients with BD included， and 19 somatic symptoms with a frequency of ＞20%， the top three being lack of strength （152 cases， 56.51%）， dry mouth （137 cases， 50.93%）， and preference for cold drinks （112 cases， 41.64%）， and the somatic symptom scores were ［7.0 （0，10.0）］ points； the YMRS scores were ［3.0 （0， 7.5）］ points； the HAMD scores were ［11.0 （5.0， 18.0）］ points； and HAMA score was ［6.0 （2.0， 10.0）］ points. Among the five-state personalities， taiyang personality ［10.0 （7.0， 13.0）］ score； shaoyang personality ［10.0 （7.5， 13.0）］ score； yin-yang balance personality ［5.0 （3.0， 7.0）］ score； shaoyin personality ［13.0 （10.0， 16.0）］ score； and taiyin personality ［14.0 （9.0， 18.0）］ score. Complex network analysis showed that BD somatic symptoms were positively correlated with taiyin personality score （r = 0.23）， HAMD score （r = 0.21）， and YMRS score （r = 0.13）； taiyin personality score was positively correlated with HAMD score （r = 0.17） and negatively correlated with YMRS score （r = -0.03）. Linear regression analyses showed that somatic symptom scores were positively correlated with HAMD score （β = 0.138， P = 0.003）， YMRS score （β = 0.128， P = 0.006）， and taiyin personality scores （β = 0.182， P＜0.001）. ConclusionDepression， mania， and taiyin personality are independent risk factors for somatic symptoms in patients with BD， and taiyin personality is strongly associated with somatic symptoms in patients with BD.

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

Objective To explore the mechanism of Prunella vulgaris and Scutellaria barbata herb pair against breast cancer based on network pharmacology and in vitro cell experiments.Methods The effective components and targets of Prunella vulgaris and Scutellaria barbata herb pair were screened.GeneCards and OMIM databases were used to find breast cancer targets,and then drug-active ingredient-key target network and protein-protein inter-action(PPI)were constructed.R language was used to perform GO function and KEGG pathway enrichment analy-sis and survival analysis.Then the screened active components and core targets were verified by molecular docking.Cell viability was detected by CCK-8 assay.EdU and flow cytometry were used to detect cell proliferation and apop-tosis.The protein expression levels of p-AKT1,AKT1,β-catenin and c-MYC were detected by Western blot.Results Through databases analysis,a total of 36 active components and 105 intersection targets were screened out,the core components were quercetin,luteolin,kaempferol,wogonin and baicalein.Through PPI and survival analysis,the key targets were AKT1,ESR1,CASP3 and MYC.GO analysis contained 4 303 enrichment results,KEGG analysis contained 232 pathways.Molecular docking showed that the core components had strong binding ability with the key targets.Cell experiments showed that the core active ingredient quercetin could inhibit the proliferation of breast cancer cells and promote their apoptosis(P＜0.05),and down-regulate the expression levels of p-AKT1,β-catenin and c-MYC proteins(P＜0.05).Conclusion The active components quercetin in Prunella vulgaris and Scutel-laria barbata herb pair may play a role through AKT1/β-catenin signaling pathway,which provides a scientific refer-ence for the study of its mechanism of action in the treatment of breast cancer.

Ankylosing spondylitis is a refractory autoimmune disease,and heterotopic ossification is one of the most important pathological features.The mechanism of heterotopic ossification in ankylosing spondylitis involves many aspects,including ossification-related genes,ossification-related factors,ossification-related cells,ossification signaling pathways,and mechanical stress.This article elaborates the pathogenesis of heterotopic ossification in ankylosing spondylitis from different aspects of multiple channels,pathways,targets,and factors,hoping to provide reference for expanding clinical and basic research and in-depth understanding of ankylosing spondylitis.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast can-