Objective: To explore the association between the cumulative effect of body mass index (BMI) in childhood and the frequency of elevated blood pressure and cumulative burden of blood pressure, so as to provide a basis for preventing high blood pressure in children. Methods: Data were derived from the "Cardiometabolic Risk Cohort Study" conducted from 2012 to 2018, which included all students from three nine year schools (comprising primary and secondary school) in Zigong City. A total of 1 583 students with normal blood pressure at baseline were included in the study. Questionnaires and physical examinations were administered to collect demographic information, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Follow up surveys were conducted annually. To measure cumulative effects, the total area under the BMI curve (BMI-AUCt), cumulative burden of SBP (CB-SBP), and cumulative burden of DBP (CB-DBP) were calculated using the trapezoidal rule. Multinomial Logistic regression models were employed to analyze the relationship between BMI-AUCt and the frequency of elevated blood pressure during the follow up period. Additionally, multiple linear regression models combined with restricted cubic splines (RCS) were used to explore the dose response relationships of BMI-AUCt with CB-SBP and CB-DBP, respectively. Results: At baseline, the median ( IQR ) values for BMI, SBP and DBP of the students were 15.0(14.2, 16.1) kg/m 2 ，89.0(87.0, 90.0) mmHg and 58.0(54.0, 60.0 ) mmHg, respectively. During follow up, the median( IQR ) BMI, SBP and DBP for students with 0, 1 and ≥2 occurrences of high blood pressure were: 14.8(14.0, 15.9), 15.2(14.3, 16.3), 15.8(14.9, 17.0) kg/m 2; 89.0(87.0, 90.0),89.0(87.0,90.0), 89.0(87.0, 90.0)mmHg; 58.0(54.0, 60.0), 58.0(54.0, 59.5), 59.0(56.0, 59.0) mmHg. Results from the multinomial Logistic regression model, after adjusting for baseline age, sex, school, overweight/obesity status and number of measurements showed that compared to students with 0 occurrence of high blood pressure during follow up, for every 1 unit increase in BMI-AUCt, the risk of having 1 occurrence and ≥2 occurrences of high blood pressure increased by 4%( OR =1.04) and 6%( OR =1.06), respectively(both P <0.05). Multiple linear regression combined with restricted cubic splines(RCS) revealed non linear dose response relationships between BMI-AUCt and both CB-SBP and CB-DBP(all P trend <0.01, all P non linearity <0.01). Specifically, BMI-AUCt was positively correlated with CB-SBP when BMI-AUCt exceeded 30.08 kg/m 2×year( β =0.13) and with CB-DBP when BMI-AUCt exceeded 48.41 kg/m 2×year( β =0.12)(both P <0.01). Conclusions Children with a higher cumulative BMI may face an increased risk of cumulative blood pressure burden. It is necessary to enhance dynamic monitoring of children s BMI and blood pressure for reducing the risk of elevated blood pressure in childhood.

Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant genetic disorder. It may also involve many other organ systems, leading to complications such as exocrine pancreatic insufficiency, liver dysfunction, lymphedema, and developmental delay. The FAM111B has been determined as the pathogenic gene associated with POIKTMP syndrome, whose protein product plays a critical role in regulating essential cellular processes including DNA repair and replication, cell cycle progression, apoptosis, nuclear transport, and telomere length maintenance. This article has provided a comprehensive review for the genetic basis of POIKTMP syndrome and its correlation with various phenotypes, which may offer insights for basic research and clinical diagnosis of this disease.
Humans ; Pulmonary Fibrosis/genetics* ; Skin Diseases, Genetic/genetics*

ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

ObjectiveTo investigate the mechanisms by which Liuwei Buqi prescription （LWBQ） regulates alveolar macrophage efferocytosis and improves inflammatory responses in rats with chronic obstructive pulmonary disease （COPD） characterized by lung-kidney Qi deficiency based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/macrophage receptor with collagenous structure （MARCO） pathway. MethodsSuccessfully modeled rats were randomly divided into a model group， low-dose LWBQ group （LWBQ-L， 2.25 g·kg^-1·d^-1）， medium-dose LWBQ group （LWBQ-M， 4.5 g·kg^-1·d^-1）， high-dose LWBQ group （LWBQ-H， 9 g·kg^-1·d^-1）， and aminophylline group （AMIN， 50 mg·kg^-1·d^-1）， with 8 rats in each group. Another 8 healthy rats were included as the blank group. Except for the blank group， rats in the remaining groups were subjected to smoke exposure combined with forced swimming， intratracheal lipopolysaccharide （LPS） instillation， and subcutaneous hydrocortisone injection to establish a COPD model with lung-kidney Qi deficiency. After successful modeling， rats were administered different doses of LWBQ or AMIN by gavage. Body weight， fur condition， and oral secretions were observed. Pulmonary function was measured using an animal lung function analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interferon-γ （IFN-γ）， interleukin-6 （IL-6）， interleukin-1 （IL-1）， and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） and serum （SER）. Hematoxylin-eosin （HE） staining was used to examine pathological changes in lung tissue. Giemsa staining was performed to detect eosinophils， basophils， and neutrophils in BALF. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was used to detect apoptosis in lung tissue. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA expression levels of efferocytosis-related proteins growth arrest-specific gene 6 （GAS6）， milk fat globule-epidermal growth factor 8 （MFG-E8）， and pathway-related proteins Nrf2 and MARCO in lung tissue. ResultsCompared with the blank group， the model group showed reduced food intake， nasal and oral secretions with sputum， and decreased body weight （P<0.01）， decreased peak expiratory flow （PEF） （P<0.01）， increased forced vital capacity （FVC） （P<0.01）， and decreased forced expiratory volume in 0.3 s/forced vital capacity ［FEV0.3/FVC （%）］ （P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were increased （P<0.01）. Lung tissue exhibited structural destruction， hyperplasia， inflammatory exudation， increased apoptotic cells， and increased mean optical density （P<0.01）. The protein and mRNA expression levels of GAS6， MFG-E8， and MARCO， as well as Nrf2 mRNA expression， were increased （P<0.01）. Compared with the model group， the LWBQ groups showed increased food intake， reduced nasal and oral secretions with sputum， and increased body weight （P<0.05， P<0.01）. PEF was increased （P<0.01）. FVC was increased in rats treated with low- and medium-dose LWBQ （P<0.01）， and FEV0.3/FVC （%） was increased in rats treated with medium- and high-dose LWBQ （P<0.05， P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were decreased （P<0.01）. Lung tissue structure was relatively intact， with improvement in hyperplasia and inflammatory exudation. The number of apoptotic cells in lung tissue was reduced， and mean optical density was decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of efferocytosis-related proteins GAS6 and MFG-E8 and pathway-related proteins Nrf2 and MARCO were increased （P<0.01）. ConclusionLWBQ can alleviate pulmonary and systemic inflammation， improve lung function， and reduce lung tissue damage in rats with COPD characterized by lung-kidney Qi deficiency. The mechanism may be related to enhancement of alveolar macrophage efferocytosis through regulation of the Nrf2/MARCO pathway.

Polycystic ovary syndrome （PCOS） is a common endocrine and metabolic disorder among women of reproductive age. Hyperandrogenism （HA）， one of its core pathological features， is closely associated with the clinical manifestations and metabolic complications of the disease. Current western medical treatments for PCOS-HA mainly include anti-androgen therapy and ovulation induction， such as short-acting oral contraceptives like Diane-35 and Yasmin. However， long-term use of these medications may result in adverse reactions like increasing the risk of liver dysfunction and exacerbating lipid metabolism disorders， with unsatisfactory long-term efficacy when used alone. Traditional Chinese medicine offers unique advantages in the treatment of PCOS-HA due to its holistic approach and multi-target regulatory mechanisms. In the view of traditional Chinese medicine， PCOS-HA is classified under the categories such as "delayed menstruation"， "amenorrhea"， and "infertility"， with kidney deficiency as the root， as well as liver stagnation and spleen deficiency as the manifestations. Phlegm and blood stasis are considered to be intertwined throughout the disease course. Modern studies have shown that traditional Chinese medicine is significantly effective in improving the androgen levels， restoring ovulation， and improving insulin resistance in PCOS-HA patients. Representative prescriptions， such as Erxian Tang， Jiawei Xiaoyaosan， Guizhi Fulingwan， and Cangfu Daotantang， exert therapeutic effects through various mechanisms including regulation of the hypothalamic-pituitary-ovarian axis， reduction of ovarian androgen synthase activity， improvement of insulin signaling pathways， and inhibition of inflammation and oxidative stress， which demonstrates the characteristics of comprehensive treatment with traditional Chinese medicine. Based on the perspectives of etiology and pathogenesis of traditional Chinese medicine， modern medical cognition， typical prescriptions， and action mechanisms， this paper reviewed the research progress of traditional Chinese medicine in the treatment of PCOS-HA， aiming to provide a reference for in-depth research and clinical applications in this field.

Polycystic ovary syndrome （PCOS） is a common endocrine and metabolic disorder among women of reproductive age. Hyperandrogenism （HA）， one of its core pathological features， is closely associated with the clinical manifestations and metabolic complications of the disease. Current western medical treatments for PCOS-HA mainly include anti-androgen therapy and ovulation induction， such as short-acting oral contraceptives like Diane-35 and Yasmin. However， long-term use of these medications may result in adverse reactions like increasing the risk of liver dysfunction and exacerbating lipid metabolism disorders， with unsatisfactory long-term efficacy when used alone. Traditional Chinese medicine offers unique advantages in the treatment of PCOS-HA due to its holistic approach and multi-target regulatory mechanisms. In the view of traditional Chinese medicine， PCOS-HA is classified under the categories such as "delayed menstruation"， "amenorrhea"， and "infertility"， with kidney deficiency as the root， as well as liver stagnation and spleen deficiency as the manifestations. Phlegm and blood stasis are considered to be intertwined throughout the disease course. Modern studies have shown that traditional Chinese medicine is significantly effective in improving the androgen levels， restoring ovulation， and improving insulin resistance in PCOS-HA patients. Representative prescriptions， such as Erxian Tang， Jiawei Xiaoyaosan， Guizhi Fulingwan， and Cangfu Daotantang， exert therapeutic effects through various mechanisms including regulation of the hypothalamic-pituitary-ovarian axis， reduction of ovarian androgen synthase activity， improvement of insulin signaling pathways， and inhibition of inflammation and oxidative stress， which demonstrates the characteristics of comprehensive treatment with traditional Chinese medicine. Based on the perspectives of etiology and pathogenesis of traditional Chinese medicine， modern medical cognition， typical prescriptions， and action mechanisms， this paper reviewed the research progress of traditional Chinese medicine in the treatment of PCOS-HA， aiming to provide a reference for in-depth research and clinical applications in this field.

OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

ObjectiveTo investigate the role of runt-related transcription factor 3 （RUNX3） in transforming growth factor-β₁ （TGF-β₁）-induced activation of mouse primary pulmonary fibroblasts （PFs）， and its effects on fibroblast activation protein （FAP） expression， cell proliferation， and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA （siRNA）. Cells were assigned to the control group （Control）， TGF-β₁-treated group （TGF-β₁）， negative control group （TGF-β₁+siRNA-NC）， and RUNX3-silenced group （TGF-β₁+si-RUNX3）. In addition， a RUNX3 overexpression rescue experiment was performed based on TGF-β₁ stimulation. Protein and mRNA levels of RUNX3， FAP， and typeⅠcollagen （COL1A1） were measured by Western blot and reverse transcription quantitative real-time PCR （RT-qPCR）. Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group， RUNX3， FAP， and COL1A1 expression levels were upregulated in PFs in the TGF-β₁ group （P<0.01）. The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group （P<0.01）. Consistently， the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group （P<0.01）. Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions， these fluorescence signals exhibited a partial rebound （P<0.01）. ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

Objective To investigate the mid- to long-term follow-up results of ascending aorta (AAO)-descending thoracic aorta (DTA) bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation. Methods A retrospective analysis was conducted on the clinical data of patients with complex aortic arch coarctation who underwent AAO-DTA bypass grafting via median sternotomy incision at the First Hospital of Tsinghua University from August 2004 to May 2017. Results A total of 7 patients were enrolled, including 4 males and 3 females, aged (13.3±4.6) years, and weighted (40.2±12.2) kg. Six (85.7%) patients had concomitant upper limb hypertension. Four patients were aortic arch coarctation combined with intracardiac malformations, two were post-operative restenosis, and 1 was post-operative restenosis combined with intracardiac malformation. All patients underwent surgery under cardiopulmonary bypass. There were no perioperative deaths or major complications. The pre-operative upper-lower limb pressure difference was (39.3±19.2) mm Hg, which decreased to (2.9±2.7) mm Hg post-operatively (P<0.01). The follow-up period was (14.9±5.9) years. There were no long-term deaths or artificial graft-related complications. Except for one patient who still had mild hypertension, the blood pressure of the remaining patients returned to normal. Conclusion AAO-DTA bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation can effectively reduce upper limb blood pressure and the upper-lower limb arterial pressure difference, has fewer complications, and demonstrates satisfactory mid- to long-term efficacy.