Child ; Humans ; Inflammatory Bowel Diseases ; Organic Anion Transporters/genetics*

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
Humans ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/adverse effects* ; Lymphoma/drug therapy* ; Lymphoma, T-Cell/therapy* ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Child ; Male ; Humans ; Female ; Child, Preschool ; Adolescent ; Crohn Disease ; Inflammatory Bowel Diseases ; Colon ; Inflammation ; Colonoscopy ; Glycoproteins ; Wnt Proteins

Objective: To explore the efficacy and safety of endoscopic diaphragm incision in pediatric congenital duodenal diaphragm. Methods: Eight children with duodenal diaphragm treated by endoscopic diaphragm incision in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from October 2019 to May 2022 were enrolled in this study. Their clinical data including general conditions, clinical manifestations, laboratory and imaging examinations, endoscopic procedures and outcomes were retrospectively analyzed. Results: Among the 8 children, 4 were males and 4 females. The diagnosis was confirmed at the age of 6-20 months; the age of onset was 0-12 months and the course of disease was 6-18 months. The main clinical manifestations were recurrent non-biliary vomiting, abdominal distension and malnutrition. One case complicated with refractory hyponatremia was first diagnosed with atypical congenital adrenal hyperplasia in the endocrinology department. After treatment with hydrocortisone, the blood sodium returned to normal, but vomiting was recurrent. One patient underwent laparoscopic rhomboid duodenal anastomosis in another hospital but had recurred vomiting after the operation, who was diagnosed with double duodenal diaphragm under endoscope. No other malformations were found in all the 8 cases. The duodenal diaphragm was located in the descending part of the duodenum, and the duodenal papilla was located below the diaphragm in all the 8 cases. Three cases had the diaphragm dilated by balloon to explore the diaphragm opening range before diaphragm incision; the other 5 had diaphragm incision performed after probing the diaphragm opening with guide wire. All the 8 cases were successfully treated by endoscopic incision of duodenal diaphragm, with the operation time of 12-30 minutes. There were no complications such as intestinal perforation, active bleeding or duodenal papilla injury. At one month of follow-up, their weight increased by 0.4-1.5 kg, with an increase of 5%-20%. Within the postoperative follow-up period of 2-20 months, all the 8 children had duodenal obstruction relieved, without vomiting or abdominal distension, and all resumed normal feeding. Gastroscopy reviewed at 2-3 months after the operation in 3 cases found no deformation of the duodenal bulbar cavity, and the mucosa of the incision was smooth, with a duodenal diameter of 6-7 mm. Conclusion: Endoscopic diaphragm incision is safe, effective and less invasive in pediatric congenital duodenal diaphragm, with favorable clinical applicability.
Male ; Child ; Female ; Humans ; Infant ; Infant, Newborn ; Retrospective Studies ; Thorax ; Endoscopy ; Physical Examination ; Adrenal Hyperplasia, Congenital

Humans ; Esophageal Achalasia/genetics* ; Cardia ; Nerve Tissue Proteins ; Nuclear Pore Complex Proteins

The present study investigated the pharmacodynamic material basis of Laportea bulbifera in the treatment of rheumatoid arthritis. Firstly, human rheumatoid arthritis fibroblast-like synoviocyte line MH7A was cultured in vitro and treated with tumor necrosis factor alpha(TNF-α, 50 ng·mL~(-1)). The proliferation and the levels of inflammatory cytokines such as prostaglandin E2(PGE2), interleukin-1β(IL-1β), and interleukin-6(IL-6) of the MH7A cells exposed to the serum containing L. bulbifera were determined to evaluate the anti-rheumatoid arthritis effects of the serum. Furthermore, the ultra-performance liquid chromatography tandem mass spectrometry fingerprints of the L. bulbifera crude extract, the drug-containing serum, and the drug-free serum were compared to identify the compounds newly generated in the serum after oral administration of the extract. According to the peak areas of common peaks and the results of anti-rheumatoid arthritis effect test, the active components were identified. The serum containing L. bulbifera significantly inhibited the proliferation of the MH7A cells activated by TNF-α and the expression of PGE2, IL-6, and IL-1β. Thirty newly generated compounds were detected in the drug-containing serum. Among them, neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, rutin, isoquercitrin, luteoloside, kaempferol-3-O-rutinoside, and quercitrin were also present in the crude extract. Twelve characteristic peaks(3, 7, 8, 14, 18, 19, 21, 23, 24, m6, m7, and m15) were significantly correlated with the pharmaceutical effect. According to the correlations, neochlorogenic acid, cryptochlorogenic acid, and chlorogenic acid had great contributions to the anti-rheumatoid arthritis activity. This study preliminarily clarified the potential pharmacodynamic substances of L. bulbifera in the treatment of rheumatoid arthritis, which laid a theoretical and experimental foundation for further development and application of the medicinal plant.
Animals ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Chlorogenic Acid/analogs & derivatives* ; Cytokines/metabolism* ; Dinoprostone ; Humans ; Interleukin-1beta/genetics* ; Interleukin-6 ; Plant Extracts/therapeutic use* ; Quinic Acid/analogs & derivatives* ; Rutin ; Tumor Necrosis Factor-alpha/metabolism* ; Urticaceae/chemistry*

Objective: To analyze the clinical features, treatment and prognosis of solitary rectal ulcer syndrome (SRUS) in children. Methods: The clinical data of 7 children who were diagnosed with SRUS in Department of Gastroenterology in Guangzhou Women and Children' Medical Center from January 2019 to December 2021 were retrospectively analyzed. The clinical data including general demographics, clinical presentations, endoscopic and histologic features, treatment and outcome were extracted from hospital medical records. Results: The 7 patients were all males, and the age of onset was 6-12 years. The course before diagnosis was 2-36 months. The most common symptom was rectal bleeding (6 cases) and most common findings at initial colonoscopy were ulcer in 3 cases and protuberance in 4 cases, both located only in rectum. The intestinal histopathology of 5 cases showed characteristic fibromuscular obliteration of lamina propria. Five children were treated with mesalamine granules or suppositories, and 2 cases underwent local excision. The follow-up lasted for 5-24 months and found symptoms relieved in 5 cases, improved in 1 case, and no remission in 1 case. Colonoscopy after the treatment was performed in 5 children, among whom 2 cases achieved mucosal healing. Conclusions: SRUS in children is mainly presented with rectal bleeding, and has characteristic histological change of ulcer and protuberance in endoscopy. Pathology is crucial for diagnosis and differential diagnosis. Both the medical and surgical treatment are effective for SRUS.
Child ; Colonoscopy ; Female ; Gastrointestinal Hemorrhage/therapy* ; Humans ; Male ; Rectal Diseases/therapy* ; Rectum/surgery* ; Retrospective Studies ; Ulcer/therapy*

【Objective】 To evaluate the effect of multi-disciplinary patient blood management(PBM) on perioperative blood transfusion in patients with cardiothoracic surgery of gradeⅢ~Ⅳ. 【Methods】 The blood transfusion data and relevant clinical information of adult patients underwent grade Ⅲ~Ⅳ cardiothoracic surgeries before and after PBM (from January 2016 to December 2018)in our hospital were collected using Hospital Information System and Management System of Blood Transfusion Department. Patients were grouped according to three separate12-month periods: 933 cases subjected to conventional blood transfusion practice from Jan. to Dec.2016 as the control group, 1 139 cases experienced initial implement PBM(started on Jan.1, 2017)from Jan. to Dec.2017 as the early PBM group, and 1 411 cases received improved PBM from Jan. to Dec.2018 as the improved PBM group. The perioperative autotransfusion rate, allogeneic transfusion rate, length of hospital stay and hospitalization expenses of the three groups were compared by χ² test and variance analysis. 【Results】 The comparison results among control group, early PBM group and improved PBM group were as following: 1) The proportion of patients using iron and EPO to treat preoperative anemia were 15.12%(44/291)vs 19.73%(72/365)vs 26.65%(125/469)(P<0.01) and 10.31%(30/291)vs 12.33%(40/365)vs 15.57%(73/469)(P<0.05), respectively. 2) The incidence of autotransfusion were 57.98%(541/933)vs 44.76%(544/1 139)vs 37.00%(522/1 411)(P<0.01). The allogeneic transfusion volume per capita(U) were 351.91±35.85 vs 392.76±43.33 vs 421.75±73.84(P<0.05). The incidence of allogeneic blood transfusion were 18.11%(169/933)vs 17.56%(200/1 139)vs 13.32%(188/1 411)(P<0.01). The allogeneic blood transfusion volume per capita (U) were 6.56±8.33 vs 5.52±6.28 vs 5.56±6.17(P<0.01). 3) The per capita hospital stay (d) and ICU stay (d) were19.54±16.56 vs 16.46±12.06 vs 15.11±10.18 and 4.45±9.31 vs 3.56±6.93 vs 3.26±5.29(P<0.05), respectively. The per capita hospitalization expenses (ten thousand yuan/person) were 10.76±8.39 vs 9.58±7.58 vs 9.13±5.9(P<0.05). 【Conclusion】 The application of PBM in perioperative blood transfusionfor adult cardiothoracic surgery Ⅲ ~ Ⅳcan significantly decrease the incidence of autologous and allogeneic blood transfusion, the length of hospitalstay and hospitalization expenses.

This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Feces ; Plant Extracts ; Rats ; Rats, Sprague-Dawley ; Urticaceae