Objective To investigate the effects of miR-139-5p-modified human umbilical cord mensenchymal stem cell(UC-MSC)-derived exosomes on stemness and radiotherapy sensitivity of breast cancer cells.Methods MCF-7 cells were divided into the control,miR-NC Exo,and miR-139-5p Exo groups.Immunofluorescence staining was used to observe the cellular uptake of exosomes.A tumor sphere formation assay determined the number of tumor spheres formed.Western blotting detected NANOG,SOX2,and OCT4 protein expression levels.MCF-7 cells were divided into control,2 Gy X ray,miR-139-5p Exo,and miR-139-5p Exo+2 Gy X ray groups.The survival rate of MCF-7 cells was detected by the MTT method.The apoptosis rate of MCF-7 cells was determined using flow cytometry.Results Compared to the control and miR-NC Exo groups,the number of tumor spheres formed by MCF-7 cells in the miR-139-5p Exo group was significantly decreased,and the relative expression levels of Nanog,SOX2,and OCT4 proteins were significantly downregulated(P＜0.05).Compared to the control group,the survival rate of MCF-7 cells in the 2 Gy X ray and miR-139-5p Exo groups was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Compared to the 2 Gy X ray group,the survival rate of MCF-7 cells in the miR-139-5p Exo+2 Gy X ray group was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Conclusion UC-MSC-derived exosomes modified by miR-139-5p inhibit the stemness of MCF-7 cells and enhance the radiotherapy sen-sitivity of MCF-7 cells.

BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

The clinical data, laboratory tests, genetic testing results, diagnosis and treatment process of a child with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome who carried an FOXP3 gene c. 748_750delAAG(p.Lys250del) variant at the Tianjin Children′s Hospital in April 2022 were analyzed retrospectively.Relevant literature was also reviewed.The typical triad of the IPEX syndrome includes intractable diarrhea, type 1 diabetes, and eczematous dermatitis.Since this syndrome is characterized by extensive clinical heterogeneity, the same mutation may have different presentations, and mutation loci are not associated with disease severity and prognosis.The patient reported in this article presented with atypical clinical symptoms without severe systemic damage.The patient developed hypogammaglobulinemia 2 years after diagnosis.The IPEX syndrome with secondary hypogammaglobulinemia usually presents in atypical cases.

The clinical data, laboratory tests, genetic testing results, diagnosis and treatment process of a child with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome who carried an FOXP3 gene c. 748_750delAAG(p.Lys250del) variant at the Tianjin Children′s Hospital in April 2022 were analyzed retrospectively.Relevant literature was also reviewed.The typical triad of the IPEX syndrome includes intractable diarrhea, type 1 diabetes, and eczematous dermatitis.Since this syndrome is characterized by extensive clinical heterogeneity, the same mutation may have different presentations, and mutation loci are not associated with disease severity and prognosis.The patient reported in this article presented with atypical clinical symptoms without severe systemic damage.The patient developed hypogammaglobulinemia 2 years after diagnosis.The IPEX syndrome with secondary hypogammaglobulinemia usually presents in atypical cases.

Objective To investigate the effects of miR-139-5p-modified human umbilical cord mensenchymal stem cell(UC-MSC)-derived exosomes on stemness and radiotherapy sensitivity of breast cancer cells.Methods MCF-7 cells were divided into the control,miR-NC Exo,and miR-139-5p Exo groups.Immunofluorescence staining was used to observe the cellular uptake of exosomes.A tumor sphere formation assay determined the number of tumor spheres formed.Western blotting detected NANOG,SOX2,and OCT4 protein expression levels.MCF-7 cells were divided into control,2 Gy X ray,miR-139-5p Exo,and miR-139-5p Exo+2 Gy X ray groups.The survival rate of MCF-7 cells was detected by the MTT method.The apoptosis rate of MCF-7 cells was determined using flow cytometry.Results Compared to the control and miR-NC Exo groups,the number of tumor spheres formed by MCF-7 cells in the miR-139-5p Exo group was significantly decreased,and the relative expression levels of Nanog,SOX2,and OCT4 proteins were significantly downregulated(P＜0.05).Compared to the control group,the survival rate of MCF-7 cells in the 2 Gy X ray and miR-139-5p Exo groups was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Compared to the 2 Gy X ray group,the survival rate of MCF-7 cells in the miR-139-5p Exo+2 Gy X ray group was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Conclusion UC-MSC-derived exosomes modified by miR-139-5p inhibit the stemness of MCF-7 cells and enhance the radiotherapy sen-sitivity of MCF-7 cells.

Objective:To summarize the clinical features and outcomes of deflazacort-induced Steven Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) to raise awareness among patients with Duchenne muscular dystrophy (DMD), neurologists as well as other deflazacort users.Methods:The clinical data of a boy with DMD who had SJS induced by deflazacort treated at the Department of Rheumatology & Clinical Immunology of Tianjin Children′s Hospital in July 2024 was analyzed retrospectively. Taking "deflazacort" "Steven-Johnson syndrome" "toxic epidermal necrolysis" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2024. The clinical characteristics, treatment and outcomes of deflazacort-induced SJS-TEN were summarized.Results:A 12-year-old boy was admitted with a 3-day history of rash. He was diagnosed with DMD at the age of 3 and had been treated with prednisolone since the age of 8. Forty-four days before admission, the patient started deflazacort to replace prednisolone. Three days before admission, progressively worsening erythematous maculopapular rashes, blisters and skin peeling (8% body surface area), oral mucosal erosion, and exudative conjunctivitis occurred, thus deflazacort was discontinued. Complete remission of SJS was achieved after treatment with intravenous immunoglobulin (IVIG, total 1.4 g/kg), 2 doses of etanercept (0.9 mg/kg, once), subcutaneous injection and intravenous methylprednisolone (0.7 mg/(kg·d)). Based on the literature, there were 5 reports in English while none in Chinese, altogether 7 cases were reported. All the patients were male, aged 3-45 years. Duration of deflazacort exposure was 2-8 weeks. Dermatology diagnosis of our case was SJS, and 5 cases were TEN. One patient was diagnosed with exudative erythema multiforme, and subsequent deflazacort oral challenge test was positive. Treatment included methylprednisolone or dexamethasone in 5 cases, IVIG in 6 cases, etanercept in 3 cases and cyclosporine in 1 case. All patients recovered completely.Conclusion:The synthetic corticosteroid deflazacort can cause rare but severe adverse reactions such as SJS-TEN, which needs close monitoring and prompt recognition and management.

Objective:To analyze the clinical characteristics of severe adenovirus pneumonia with bacterial infection in children, so as to provide clinical evidences for early diagnosis and reliable treatment.Methods:A total of 72 pediatric cases with severe adenovirus pneumonia admitted to Pediatric Intensive Care Unit at the First People′s Hospital of Chenzhou from January 2018 to August 2019 were included.The clinical features, laboratory and imaging data, efficacy of the treatments and prognosis were investigated retrospectively.Patients were divided into with bacterial infection group and without bacterial infection group.The clinical characteristics were analyzed.Results:Among the 72 children, there were 54 males and 18 females, aging from 3 months to 5 years, including 37cases with bacterial infection and 35 cases without bacterial infection.Compared with the group without bacterial infection, the group with bacterial infection had longer heat duration and hospital stay [12.0 (10.0, 18.5) days vs.10.0 (9.0, 12.0) days; 6.0(4.0, 7.0) days vs.11.0(6.5, 16.0) days, P<0.05], the incidences of diarrhea and hepatomegaly were higher[35.1% (13/37) vs.14.3%(5/35); 45.9%(17/37)vs.8.6%(3/35), P<0.05], the proportion of five lobes involved in lung imaging was higher [91.8% (34/37) vs. 57.1%(20/35), P<0.05]. The incidences of complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans in the group with bacterial infection were significantly higher than those of without bacterial infection group ( P<0.05). Conclusion:For children under 2 years old age with severe adenovirus pneumonia, there are prolonged high fever and extensive pulmonary lesions.We should be highly alert to the combination of bacterial infection and timely anti-infection therapy.Children with severe adenovirus pneumonia with bacterial infection have severe clinical manifestations and many complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans.

Objective:To observe the distribution ratio of histiocytic necrotizing lymphadenitis(HNL) in the age of children, evaluate glucocorticoids and Hydroxychloroquine therapeutic effects, evaluate the meaning of lymph node excisional biopsy.Methods:The data of 70 cases of patients with the lymph node excisional biopsy in Tianjin Children′s Hospital from December 2010 to August 2019 were retrospectively analyzed.and summarized the treatment experience and prognosis.Results:HNL mostly occurs in children 7-12 years old.The male-female ratio was 1.12∶1.00, but over 13 years old was 0.6∶1.0.Eighteen point one six percent (13 cases) of HNL was relieved after the lymph node excisional biopsy.Thirty-five cases were treated with non-steroidal anti-inflammatory drugs (NSAIDs), and only 10 cases (14.2%) were improved with NSAIDs alone and the rest were improved in combination with glucocorticoids.Four patients with ineffective glucocorticoids therapy were improved in combination with Hydroxychloroquine.Conclusion:HNL in children was more common in school-age children.For children under 13 years old, the incidence among boys is slightly higher than that among girls; for children above 13 years old, the incidence among boys is slightly lower than that among girls.Lymph node biopsy is still the gold standard for diagnosis and is conducive to remission.The course of disease is self-limited, for the cases that NSAIDs is poor, the glucocorticoid treatment should be used.For refractory cases, combined Hydroxychloroquine treatment can be used.

OBJECTIVE: To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. METHODS: Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. RESULTS: The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. CONCLUSIONS Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Angiotensin II Type 1 Receptor Blockers ; Animals ; Antihypertensive Agents ; Extracellular Matrix Proteins ; metabolism ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; Random Allocation ; Telmisartan ; pharmacology ; Transforming Growth Factor beta1 ; pharmacology ; Ureteral Obstruction ; complications ; metabolism

Objective: To investigate the clinical application of indocyanine green fluorescence imaging in open hepatectomy. Methods: A total of forty-five patients who underwent liver resection in Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University from July 2017 to December 2018 were included in this prospective study. There were 26 males and 19 females, aged between 29 to 74 (51±10) years. Indocyanine green was injected intravenously 72~96 hours prior to surgery in all these patients. An intraoperative fluorescence imaging system was used to locate and remove the tumor, the liver parenchymal transection planes and surgical margins were detected by fluorescence again after tumor resection. The fluorescence profiles of the tumor specimens in relation to the tumor differentiation were analyzed. Results: Indocyanine green fluorescence imaging was performed in 45 patients. A total of 66 lesions were detected by preoperative CT (or MRI), abdominal ultrasound and intraoperative fluorescence imaging. After excision of the primary liver cancer, the surgical margins of the remnant liver stumps and fluorescence in the excised liver specimens were studied. Thirteen small lesions were found in 10 patients, most of which were located at the surgical margin, and the smallest tumors detected were less than 5 mm in diameter. Five venous cancer emboli were found in 5 patients, 3 of which were not detected by preoperative imaging examinations. The fluorescence profile images of the excised hepatocellular carcinoma specimens showed homogeneous fluorescence in most highly differentiated hepatocellular carcinoma, and partial fluorescence or ring fluorescence in moderately differentiated hepatocellular carcinoma. Conclusion Indocyanine green fluorescence imaging technology can identify liver surface lesions, as well as detect small residual lesions at the cutting edge and venous thrombus, which improves the efficiency of hepatocellular carcinoma resection.