Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

Haematitum and Limonitum are two iron-containing mineral medicines included in the 2020 edition of the Chinese Pharmacopoeia. They have similar main components and major differences in their property, flavor, channel tropism, and clinical uses. In this study, we investigated the surface properties, mineral composition, mineral dissociation, elemental composition, and iron state of Haematitum and Limonitum to explore their mineralogical differences. Scanning electron microscopy(SEM), specific surface and porosity analyzer, X-ray diffractometer(XRD), X-ray photoelectron spectrometer(XPS), and advanced mineral identification and characterization system(AMICS) were used to analyze the mineralogy of Haematitum and Limonitum. The results showed that Haematitum had an angular surface with granular attachments and a specific surface area of 17.04 m~2·g~(-1). In comparison, Limonitum had a smooth and flat surface with a bundled acicular crystal structure and a specific surface area of 46.29 m~2·g~(-1). Haematitum consists of 31 detectable minerals containing 18 elements, with the major element, iron(44.5% Fe~(2+) and 55.5% Fe~(3+)) distributed in 17 minerals, including hematite, iron oxide, knebelite, siderite, and magnesioferrite. Limonitum consists of 32 detectable minerals containing 17 elements, with the major element, iron(14.5% Fe~(2+) and 85.5% Fe~(3+)) distributed in 19 minerals, including limonite, iron oxide, chlorite, and knebelite. In summary, the elemental composition of Haematitum and Limonitum does not differ greatly, but there are large differences in the mineral composition and iron state. The large specific surface area and strong adsorption capacity of Limonitum may be one of the mechanisms of its anti-diarrheal action. The Fe_2O_3 and illite contained in Haematitum and Limonitum may be the key substances for their hemostasis effects. The mineralogical differences are expected to provide a reference for explaining the scientific connotation of mineral medicine and laying a material foundation for studying its mechanism of action.
Iron/analysis* ; Minerals/chemistry* ; Drugs, Chinese Herbal/chemistry* ; X-Ray Diffraction ; Microscopy, Electron, Scanning ; Photoelectron Spectroscopy

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the expression of small nuclear ribonucleoprotein D1 (SNRPD1) in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1. Methods The UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway. Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer (P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue (P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen (P<0.001),carbohydrate antigen 19-9 (P<0.001),G stage (P=0.042),T stage (P=0.002),and N stage (P=0.027) in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer (P<0.001),and it was an independent risk factor for the death of gastric cancer patients (P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed that SNRPD1 was involved in the regulation of the cell cycle.The results of CCK-8 and colony formation assays showed that up-regulation of SNRPD1 promoted the proliferation of gastric cancer cells (P<0.001,P<0.001).The up-regulation of SNRPD1 up-regulated the expression of cyclin-dependent kinase 6 and G₁/S-specific cyclin-D1 (P<0.001,P=0.002),whereas the interference in SNRPD1 led to opposite results (P=0.004,P<0.001).SNRPD1 accelerated the G₁/S phase transition of gastric cancer cells (P<0.001).The overexpression of SNRPD1 promoted the expression of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in gastric cancer cells (P=0.043,P<0.001),whereas disruption of SNRPD1 inhibited their expression (both P<0.001).Insulin-like growth factor 1,an agonist of the PI3K/Akt signaling pathway,promoted the proliferation of gastric cancer cells with SNRPD1 disturbed (P=0.002). Conclusion High expression of SNRPD1 in the gastric cancer tissues is associated with poor prognosis,and it may promote tumor cell proliferation and regulate the cell cycle by activating the PI3K/Akt signaling pathway.
Humans ; Stomach Neoplasms/pathology* ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Retrospective Studies ; Cell Cycle ; Male ; Female

Objective To investigate the rate of greater omentum metastasis in gastric cancer(GC). Methods General informations of patients with GC who underwent radical gastrectomy at Shanghai Ruijin Hospital in May 2020 were collected, and their clinicopathological characteristics were analyzed to find risk factors of greater omentum metastasis. Recurrence and survival were also assessed. Results A total of 59 patients with GC were included in the study, of which 2(3.4%) had greater omentum metastasis. One patient presented a pathological stage of pT4aN3bM0 and another ypT4bN1M0. The 3-year overall survival rate of patients in the study was 87.9%. Conclusions The rate of greater omentum metastasis was relatively low, and patients with greater omentum metastasis had an more advanced pathological stage. To further validate this clinical issue, a prospective randomized controlled clinical study should be conducted between radical gastrectomy with omentectomy and omentum-preserving radical gastrectomy.

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVE: To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia (AML) cells and its molecular mechanism, so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine. METHODS: The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients, cell proliferation was detected by CCK-8 method, morphological changes were detected by Wright-Giemsa method, apoptosis was detected by Annexin V/PI double staining flow cytometry, and apoptosis and signal pathway protein expression were detected by Western blot. Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins (SOX). RESULTS: Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells, up-regulated the expression of pro-apoptotic protein Bax, down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin, and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells. Thymoquinone could also significantly down-regulate the phosphorylation of PI3K, Akt and mTOR, and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway. After thymoquinone intervention in HL-60 and THP-1 cells, the expression of SOX2 and SOX4 could be down-regulated significantly. At low concentration ( < 10 μmol/L), the expression of SOX12 was weakly affected by thymoquinone. With increasing concentration, the expression of SOX12 could be down-regulated, however, thymoquinone had no effect on SOX11 expression. CONCLUSION Thymoquinone can inhibit the proliferation of AML cells, and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway, regulating the expression of apoptotic proteins and core members of SOX family.
Humans ; Benzoquinones/pharmacology* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/metabolism* ; Apoptosis/drug effects* ; HL-60 Cells ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/metabolism* ; THP-1 Cells

OBJECTIVE: To investigate the regulatory effect of Wip1 phosphatase on hematopoietic function in the mouse spleen. METHODS: Wip1 knockout mice were bred, and the effect of Wip1 deletion on the proportion and number of hematopoietic stem/progenitor cells, as well as their mature subsets in mouse spleen was detected by flow cytometry. The Proteome Profiler^TM antibody array was used to analyze the role of Wip1 deletion on the expression of inflammatory cytokines in CD45^highCD11b⁺ myeloid cells sorted from mouse spleen. RESULTS: Wip1 deletion resulted in smaller size and significant reduction of cell number in the mouse spleen. The absolute numbers of hematopoietic stem/progenitor cells were decreased. Meanwhile, the absolute number of T and B lymphocytes also significantly declined. However, the proportion of erythroid progenitors and erythroid cells at various stage significantly increased, but the number of mature erythroid cells decreased. Furthermore, the myeloid cells and their subsets neutrophils, monocytes, CD45^highCD11b⁺ and CD45^lowCD11b⁺ were all reduced. CD45^highCD11b⁺ myeloid cells displayed proinflammatory phenotype in the spleen. CONCLUSION Wip1 gene deletion impairs normal hematopoietic function in the mouse spleen, leading to a significant reduction of mature hematopoietic cells of various lineages, and proinflammatory phenotype in CD45^highCD11b⁺ myeloid cells.
Animals ; Mice ; Spleen/cytology* ; Mice, Knockout ; Hematopoietic Stem Cells/cytology* ; Myeloid Cells/cytology* ; Protein Phosphatase 2C ; Hematopoiesis ; Flow Cytometry