Objective: To analyze the trajectories of body mass index for age z-score (BAZ) and its influencing factors among children with congenital hypothyroidism (CH) based on latent class growth modeling (LCGM), so as to provide the evidence for improving treatment measures and optimizing growth management among children with CH. Methods Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Methods: Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Results: A total of 299 children with CH were included. There were 140 boys (46.82%) and 159 girls (53.18%). The median of BAZ was 0.50 (interquartile range, 1.68). The LCGM analysis categorized the subjects into three groups: the persistent high-growth pattern group with 24 cases (8.03%), the slow-growth pattern group with 39 cases (13.04%), and the appropriate-growth pattern group with 236 cases (78.93%). Multinomial logistic regression analysis showed that compared to the children with CH in the appropriate-growth pattern group, those who started treatment at the age of 30 to 60 days (OR=0.109, 95%CI: 0.016-0.732; OR=0.166, 95%CI: 0.032-0.852) had a lower risk of persistent high-growth and slow-growth patterns; CH children with TSH levels of 50 to 150 mIU/L at diagnosis (OR=3.554, 95%CI: 1.201-10.514) and those whose paternal had a senior high school/technical secondary school education (OR=2.975, 95%CI: 1.003-8.823) exhibited a higher risk of the persistent high-growth pattern. Conversely, CH children whose paternal reproductive age was 30 to 35 years (OR=0.166, 95%CI: 0.034-0.806) had a lower risk of the persistent high-growth pattern. Conclusions The BAZ trajectory of children with CH aged 0 to 3 years exhibited three patterns: persistent high-growth, slow-growth, and appropriate-growth. The persistent high-growth and slow-growth patterns were associated with treatment timing, TSH levels at diagnosis, paternal reproductive age, and paternal education level. It is recommended to strengthen early treatment interventions and provide family follow-up guidance.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Spinocerebellar ataxia (SCA) is a group of progressively aggravated neurodegenerative disease with autosomal dominant inheritance. Cerebellar ataxia is the core symptom, which may be accompanied by pyramidal tract signs, extrapyramidal signs, cognitive dysfunction and peripheral neuropathy. Although SCA can be accurately diagnosed by genetic testing, treatment is still difficult. We review the pathogenesis and therapeutic targets of SCA in recent years, in terms of genetic or gene regulation abnormalities, disruption of protein quality control (PQC) network, disruption of energy homeostasis, stability maintenance of PQC system, maintenance of cerebellar Purkinje cell function, and regulation of neuroinflammation, so as to promote the transformation of preclinical research into human therapy.

Based on the physiological and pathological characteristics of"spleen is often insufficient"in Children,Professor Jiang Yuren put forward the academic view of"the health of the spleen is not replenished but regulated",and took"spleen regulation meth-od"as the first choice for the treatment of spleen-stomach diseases such as anorexia,diarrhea,infantile malnutrition,iron deficiency anemia.By systematically analyzing the academic connotation,clinical practice,inheritance and development of Professor Jiang Yuren's"spleen regulation method"and combining with the current research progress,this article interprets the internal molecular mechanism of"spleen regulation method"to provide scientific basis for further promoting the clinical application and modern research of Professor Jiang Yuren's"spleen regulation method".

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

Objective:To explore the genetic basis for a fetus with increased risk for Down syndrome and cardiac anomalies discovered by prenatal ultrasonography.Methods:A pregnant woman presented at the Women and Children′s Hospital of Ningbo University on August 21, 2023 were selected as the study subject. Clinical data were retrospectively analyzed. Maternal peripheral blood sample was collected for non-invasive prenatal testing (NIPT) based on fetal free DNA. Amniotic fluid sample was collected for G-banded chromosomal karyotyping analysis. Trio-whole exome sequencing (WES) was also carried out on the amniotic fluid sample and peripheral blood samples from the couple. Copy number variation (CNV) identified by the WES was validated by real-time fluorescent quantitative PCR (qPCR). Chromosomal karyotyping was also carried out for the couple. This study has been approved by the Medical Ethics Committee of Women and Children′s Hospital of Ningbo University (No. EC2020-048).Results:Ultrasound examination at 22 + 6 gestational weeks had indicated intrauterine growth retardation (IUGR). The fetus was also found to have ventricular septal defect, overriding aorta and pulmonary stenosis. NIPT indicated a low risk for aneuploidy of chromosomes 13, 18 and 21. G-banding analysis revealed that the fetus had a karyotype of 45, XY, -2[5]/46, XY, r(2)(p25q37)[55]. WES has identified a deletion of approximately 1 614.28 kb in the 2p25.3 region, namely seq[hg38]del(2)(p25.3p25.3)chr2: g.10500_1624775del. The same deletion was found in neither parent, suggesting a de novo origin. qPCR results confirmed the expression of target genes in the fetal sample to be significantly reduced, whilst no similar anomaly was found in either parent. Conclusion:The mosaicism ring chromosome 2 probably underlay the IUGR and cardiovascular malformations in this fetus.

Objective To analyze the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy,and to explore the adverse effects of sarcopenia on patients with ad-vanced lung cancer undergoing anti-tumor therapy.Methods Patients with advanced lung cancer who received anti-tumor therapy in the Department of Oncology of a tertiary hospital in Chengdu from January to December 2021 were continuously included.The incidence situation of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy was evaluated by using the 12th thoracic spine (T12) skeletal muscle index (SMI) standard.According to the diagnostic criteria of sarcopenia,the patients were divided into the sarcope-nia group and the non-sarcopenia group.Multivariate logistic regression was used to analyze the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy.Results A total of 285 patients were included in this study,of which 123 cases (43.15％) were diagnosed as sarcopenia.Multiva-riate analysis showed that gender (P<0.001),pathological stage (P=0.012),creatinine (P=0.031) and BMI (P<0.001) were the influencing factors of sarcopenia in patients with advanced lung cancer undergoing anti-tumor therapy.The quality of life score of patients in the sarcopenia group was significantly lower than that in the non-sarcopenia group (P=0.035).Conclusion The incidence of sarcopenia in patients with ad-vanced lung cancer undergoing anti-tumor therapy is high,which is related to many factors and affects the quality of life.

A clinically serious illness with a high death and morbidity rate is sepsis.Electro-acupuncture is a significant adjuvant treatment for sepsis,lowering the inflammatory response to sepsis,regulating the patient's immunological function,and preventing multi-system organ damage.However,no comprehensive study has been published.In order to review the clinical application of electro-acupuncture in the field of sepsis and its complications,analyze its clinical efficacy,and summarize effective acupuncture point prescriptions,we systematically compiled the clinical research literature on electro-acupuncture in the treatment of sepsis and its complications by searching PubMed,CNKI,and other databases.It was found that effective clinical evidence had been gathered for the administration of electro-acupuncture in uncomplicated sepsis as well as in sepsis aggravated by gastrointestinal,pulmonary,cardiac,and brain injury.The following successful acupoint prescriptions were indicated:①Simple sepsis was treated with"Zusanli+Guanyuan"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";②Combined gastrointestinal injury was treated with"Zusanli+Shangjuxu+Tianshu"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";③ Combined lung injury was treated with"Zusanli+Chize";④Combined myocardial injury was treated with"Neiguan+Zusanli+Shenmen+Taichong+Xuehai+Geshu+Sanyinjiao+Hegu";⑤Combined brain injury was treated with"Baihui+Shuigou".The study's findings can offer preliminary clinical direction for using electro-acupuncture to treat sepsis and associated complications in patients.