ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

BACKGROUND:Preliminary research by our group suggests that targeting fibroblast growth factor receptor 1(FGFR1)may be an effective strategy for treating RA. OBJECTIVE:To investigate the effects of an FGFR1 inhibitor(PD173074)on bone destruction in rats with collagen-induced arthritis. METHODS:Twenty-five female Sprague-Dawley rats were randomly divided into five groups:normal control group,model group,methotrexate group,low-dose PD173074 group,and high-dose PD173074 group.Except for the normal control group,rat models of type Ⅱ collagen-induced arthritis were made in each group.After successful modeling,rats were injected intraperitoneally with sterile PBS in the normal and model groups,1.04 mg/kg methotrexate in the methotrexate group,and 5 and 20 mg/kg in the low-dose group and high-dose PD173074 groups,once a week.After 4 weeks of drug administration,clinical symptoms and joint swelling in rats were observed.Micro-CT was used for three-dimensional reconstruction and analysis of the ankle joints.Pathological changes in the ankle joints were observed.Periarticular angiogenesis and the expression of receptor activator of nuclear factor-Κb ligand were detected.The expression levels of p-FGFR1,vascular endothelial growth factor A,and tartrate-resistant acid phosphatase in the synovial membrane were measured.Pathological changes in the liver,spleen,and kidney were observed and liver,spleen,and kidney indices were calculated. RESULTS AND CONCLUSION:PD173074 could alleviate clinical symptoms and joint swelling,delay bone loss,improve bone structure,reduce synovial invasion and cartilage bone erosion,reduce the number of periarticular osteoclasts,inhibit angiogenesis in synovial tissues,reduce the expression of receptor activator of nuclear factor-Κb ligand,and inhibit the expression of FGFR1 phosphorylated protein,tartrate-resistant acid phosphatase and vascular endothelial growth factor A.Pathologic observation of the liver,spleen and kidney in rats showed no obvious toxic side effects after PD173074 treatment.To conclude,the FGFR1 inhibitor can delay the progression of joint inflammation and bone destruction and inhibit angiogenesis in the rat model of type Ⅱ collagen-induced arthritis.The therapeutic effect of PD173074 has been preliminarily validated in the type Ⅱ collagen-induced arthritis model and may act by inhibiting FGFR1 phosphorylation,which provides a direction for the search of new therapeutic targets for rheumatoid arthritis.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Cardiovascular diseases （CVD），a group of common diseases in clinical practice，are witnessing a steady rise in both incidence and mortality rates，posing a challenge to public health. Gualou Xiebai Banxiatang，originating from Synopsis of the Golden Chamber （《金匮要略》），was initially used to treat severe cases of chest impediment. The formula consists of Trichosanthis Fructus，Allii Macrostemonis Bulbus，Pinelliae Rhizoma，and Baijiu. It has a wide range of clinical applications，with therapeutic effects including moving Qi to relieve depression，activating Yang to dissipate mass，and expelling phlegm to alleviate chest congestion. In recent years，clinical research has confirmed that Gualou Xiebai Banxiatang，with or without modification，used alone or in combination with Western medicine，has definite effects in the treatment of CVD such as hyperlipidemia，coronary atherosclerotic heart disease，hypertension，heart failure，and arrhythmia. It can alleviate disease symptoms and reduce the risk of re-hospitalization. Basic research indicates that the mechanisms of Gualou Xiebai Banxiatang include improving endothelial functions，exhibiting anti-inflammatory properties，countering oxidative stress，preventing apoptosis，inhibiting ventricular remodeling，regulating mitochondrial functions，improving hemorheology，and modulating autophagy and neurotransmitters. This article reviews relevant articles in recent years with focuses on the compatibility，clinical application，and mechanism of Gualou Xiebai Banxiatang. This review is expected to provide a theoretical basis for the mechanism research and clinical application of this formula in treating CVD and to offer ideas and reference for in-depth research.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

OBJECTIVES: To investigate the clinical characteristics and prognosis of infants and young children with basal ganglia infarction after minor head trauma (BGIMHT). METHODS: A retrospective analysis was conducted on the clinical data and follow-up results of children aged 28 days to 3 years with BGIMHT who were hospitalized at Children's Hospital of Soochow University from January 2011 to January 2022. RESULTS: A total of 45 cases of BGIMHT were included, with the most common symptom being limb movement disorders (96%, 43/45), followed by facioplegia (56%, 25/45). Cerebral imaging showed that 72% (31/43) had infarction accompanied by basal ganglia calcification. After conservative treatment, 42 children (93%) showed significant symptom improvement, while 3 children (7%) experienced recurrent strokes. The median follow-up time was 82 months (range: 17-141 months). At the last follow-up, 97% (29/30) had residual basal ganglia softening lesions. Among 29 cases participating in questionnaire follow-up, 66% (19/29) recovered normally, 17% (5/29) showed significant improvement in symptoms, and 17% (5/29) had poor improvement. According to the grading of the Global Burden of Disease Control Projects, only 1 child (3%) had severe sequelae. There were no significant differences in age at onset, gender, or presence of concomitant basal ganglia calcification between children with and without neurological sequelae (P>0.05). CONCLUSIONS The most common initial symptom of BGIMHT is limb movement disorder, and imaging results indicate that most children have concurrent intracranial calcifications. Most infarct lesions later transform into softening lesions, resulting in a generally good prognosis.
Humans ; Male ; Female ; Infant ; Child, Preschool ; Craniocerebral Trauma/complications* ; Follow-Up Studies ; Retrospective Studies ; Basal Ganglia/pathology* ; Infant, Newborn

OBJECTIVES: To study the differences in clinical characteristics of term and preterm neonates with necrotizing enterocolitis (NEC) undergoing surgical treatment. METHODS: A retrospective analysis was conducted on the clinical data of 142 NEC neonates who underwent surgery at the Children's Hospital of Chongqing Medical University from June 2017 to August 2023. The neonates were categorized into a preterm group (gestational age <37 weeks; 95 cases) and a term group (gestational age 37-42 weeks; 47 cases) to compare clinical characteristics. RESULTS: The preterm group had a higher postnatal age at both diagnosis and surgery compared to the term group (P<0.05). The preterm group also had a higher incidence of preoperative bloody stools, lower preoperative platelet counts, and higher rates of preoperative respiratory distress, apnea, reduced/absent bowel sounds, and mechanical ventilation compared to the term group (P<0.05). Postoperatively, the preterm group had higher rates of purulent meningitis, sepsis, and coagulation dysfunction, lower postoperative platelet counts, and lower intraoperative minimum body temperature than the term group (P<0.05). CONCLUSIONS There are significant differences in the clinical characteristics of preterm and term neonates with NEC undergoing surgery, suggesting the need for tailored perioperative management strategies based on these characteristics.
Humans ; Enterocolitis, Necrotizing/surgery* ; Infant, Newborn ; Retrospective Studies ; Male ; Female ; Infant, Premature ; Gestational Age

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide