A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective: To analyze the relationship between body mass index(BMI) during pre pregnancy, maternal lipid levels during early pregnancy and childhood overweight and obesity, as well as the mediating role of maternal lipid levels during early pregnancy in pre pregnancy BMI and childhood overweight and obesity, providing scientific evidence for developing obesity prevention strategies in preschool children. Methods: Using data from Peking University Birth Cohort in Tongzhou (PKUBC-T) collected between June 2018 and September 2022, the study included 1 292 mother-child pairs. Participants were stratified into two groups based on children s BMI Z scores at age 3: an overweight/obesity risk group (BMI Z >1, n =173) and a non overweight/obesity risk group (BMI Z ≤1, n =1 119).Multivariate Logistic regression was conducted to analyze the associations between pre pregnancy BMI, maternal lipid levels[total cholesterol(TC),triglyceride（TG）,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),TC/HDL-C,TG/HDL-C,LDL-C/HDL-C] during early pregnancy and childhood overweight and obesity. The mediating effect of maternal lipid levels during early pregnancy on pre pregnancy BMI and childhood overweight and obesity was further explored. Results: There were statistically significant differences in pregnancy BMI levels, early pregnancy blood LDL-C ,TC/HDL-C,LDL-C/HDL-C levels between the overweight and obesity risk group and the non overweight and obesity risk group ( χ 2/Z =19.01, 2.48, 2.48, 2.71, all P <0.05). Multivariate Logistic regression analysis showed that pre pregnancy BMI, LDL-C, TC/HDL-C and LDL-C/HDL-C in early pregnancy were significantly associated with childhood overweight and obesity ( OR =1.09, 1.42, 1.49, 1.60, all P <0.05). LDL-C, TC/HDL-C and LDL-C/HDL-C in early pregnancy played a significant mediating role on pre pregnancy BMI and childhood obesity and the mediating effects accounted for 7.3%, 10.2%, 23.5% of the total effects, respectively (all P <0.05). Conclusions Maternal hyperlipidemia during early pregnancy partially mediated the association between pre pregnancy obesity and childhood obesity. Both pre pregnancy obesity and maternal hyperlipidemia during early pregnancy are risk factors for obesity in preschool children.

ObjectiveTo investigate the efficacy and mechanism of Polygoni Cuspidati Rhizoma et Radix （Huzhang） in treating respiratory syncytial virus（RSV） infection by regulating pulmonary surfactant lipid homeostasis through lipidomics. MethodsSixty BALB/c mice were randomly divided into the blank group， model group， positive group（ribavirin group， 46 mg·kg^-1）， and low- and high-dose Huzhang groups（0.75， 2.25 g·kg^-1）， with 12 mice in each group. Except for the blank group， all other groups were infected with RSV via intranasal instillation. The drug intervention groups were given corresponding doses of drug by gavage for 3 consecutive days， while normal saline was used in the blank and model groups. Hematoxylin-eosin（HE） staining was used to observe pathological changes in mouse lung tissue. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect viral loads［RSV-nucleoprotein（N） and RSV-glycoprotein（G） mRNA］ and inflammatory factor levels［interleukin（IL）-1β and tumor necrosis factor（TNF）-α mRNA］ in the lung tissue. Mouse bronchoalveolar lavage fluid was collected to detect the levels of pulmonary surfactant lipids through ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， followed by principal component analysis and differential lipid identification. ResultsCompared with the blank group， the model group exhibited extensive inflammatory cell infiltration， congestion， and tissue damage in the lungs， and the pathological score and lung index of lung tissue significantly increased（P<0.01）， along with significantly elevated mRNA expressions of RSV-N， RSV-G， IL-1β， and TNF-α（P<0.01）. Compared with the model group， different doses of Huzhang and ribavirin significantly reduced the pathological scores of the lung tissue and lung index（P<0.01）. In addition， the mRNA levels of RSV-N， RSV-G and TNF-α in the lungs significantly decreased in the Huzhang high dose group（P<0.01）. Lipidomics analysis identified multiple significantly changed differential metabolites. Compared with the blank group， the model group showed obvious abnormal lipid metabolism， which was manifested by the elevated levels of prostaglandin（PG）， ceramide（Cer）， phosphatidylcholine（PC）， phosphatidylethanolamine（PE）， phosphatidylinositol（PI）， sphingomyelin（SM）， and the decreased levels of diglycerides（DG） and acylethanolamine（NAE）. After the intervention of low dose of Huzhang， the above lipid metabolites showed a significant reversal trend， while the intervention of high dose of Huzhang could regulate levels of PI lipids， PG lipids and PC lipids. ConclusionHuzhang can significantly reduce the viral load of lung tissue and improve lung inflammation in RSV-infected mice. The underlying mechanism may be related to the maintenance of homeostasis in pulmonary surfactant lipids such as PI and PG.

ObjectiveTo investigate the efficacy and mechanism of Polygoni Cuspidati Rhizoma et Radix （Huzhang） in treating respiratory syncytial virus（RSV） infection by regulating pulmonary surfactant lipid homeostasis through lipidomics. MethodsSixty BALB/c mice were randomly divided into the blank group， model group， positive group（ribavirin group， 46 mg·kg^-1）， and low- and high-dose Huzhang groups（0.75， 2.25 g·kg^-1）， with 12 mice in each group. Except for the blank group， all other groups were infected with RSV via intranasal instillation. The drug intervention groups were given corresponding doses of drug by gavage for 3 consecutive days， while normal saline was used in the blank and model groups. Hematoxylin-eosin（HE） staining was used to observe pathological changes in mouse lung tissue. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect viral loads［RSV-nucleoprotein（N） and RSV-glycoprotein（G） mRNA］ and inflammatory factor levels［interleukin（IL）-1β and tumor necrosis factor（TNF）-α mRNA］ in the lung tissue. Mouse bronchoalveolar lavage fluid was collected to detect the levels of pulmonary surfactant lipids through ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， followed by principal component analysis and differential lipid identification. ResultsCompared with the blank group， the model group exhibited extensive inflammatory cell infiltration， congestion， and tissue damage in the lungs， and the pathological score and lung index of lung tissue significantly increased（P<0.01）， along with significantly elevated mRNA expressions of RSV-N， RSV-G， IL-1β， and TNF-α（P<0.01）. Compared with the model group， different doses of Huzhang and ribavirin significantly reduced the pathological scores of the lung tissue and lung index（P<0.01）. In addition， the mRNA levels of RSV-N， RSV-G and TNF-α in the lungs significantly decreased in the Huzhang high dose group（P<0.01）. Lipidomics analysis identified multiple significantly changed differential metabolites. Compared with the blank group， the model group showed obvious abnormal lipid metabolism， which was manifested by the elevated levels of prostaglandin（PG）， ceramide（Cer）， phosphatidylcholine（PC）， phosphatidylethanolamine（PE）， phosphatidylinositol（PI）， sphingomyelin（SM）， and the decreased levels of diglycerides（DG） and acylethanolamine（NAE）. After the intervention of low dose of Huzhang， the above lipid metabolites showed a significant reversal trend， while the intervention of high dose of Huzhang could regulate levels of PI lipids， PG lipids and PC lipids. ConclusionHuzhang can significantly reduce the viral load of lung tissue and improve lung inflammation in RSV-infected mice. The underlying mechanism may be related to the maintenance of homeostasis in pulmonary surfactant lipids such as PI and PG.

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*