Abstract Cardiovascular disease is one of the leading causes of death worldwide, and myocardial remodeling is at the core of the development and progression of most cardiovascular diseases. Purinergic ligand-gated ion channel 7 receptor(P2X7R) is a member of the purinergic receptor family, which is expressed in immune cells, cardiac smooth muscle cells, and endothelial cells, and plays an important role in pathological processes related to immune system regulation, neuroprotection, and inflammatory responses. Activation of P2X7R plays an important role in myocardial remodeling, including myocardial fibrosis, myocardial hypertrophy, and heart failure. Therefore, this article reviews the structural and functional properties of P2X7R and its mechanism of action in myocardial remodeling.

SWOT-PEST model was used to analyze the internal advantages and disadvantages,external,opportunities and challenges of tertiary public pediatric hospitals.Based on stakeholder theory,through the literature review method,policy analysis method,combined with the actual work,and summarize its main role and demands.Put forward the development strategy of three-level public pediatric specialty hospital.Through the analysis of interest demands of stakeholders of tertiary public pediat-ric specialty hospitals,the overall development is good at present,but there are still problems that need to be solved urgently.From the perspective of internal and external stakeholders,the optimization strategy involving multiple levels,multiple angles and multiple subjects is proposed to promote the comprehensive development of tertiary public pediatric specialty hospitals.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To identify and analyze different proteins expression in the periosteum of congenital pseudarthrosis of the tibia (CPT) using tandem mass tags (TMT) proteomics.Methods:The samples were divided into three groups, namely CPT with neurofibromatosis type 1 (NF1) group (NF1-CPT group), CPT without NF1 group (nonNF1-CPT group) and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 was regarded as the threshold to screen differentially expressed proteins (DEPs). Subsequently, bioinformatics resources such as online tools DAVID and STRING were used to conduct GO annotation, KEGG pathways enrichment and protein-protein interaction (PPI) network with DEPs. Results:A total of 347 proteins differentially expressed in NF1-CPT group, 212 of which were up-regulated and 135 down-regulated. We identified 467 DEPs in nonNF1-CPT group, including 281 up-regulated and 186 down-regulated. Among of them, NF1-CPT group and nonNF1-CPT group shared 231 DEPs, except for HLA-DRB1 which increased in NF1-CPT group but decreased in nonNF1-CPT group. The remaining 230 DEPs showed the same expression trend in the two positive groups, including 117 up-regulated and 113 down-regulated. In particular, a total of 116 proteins were altered only in NF1-CPT group, including 94 up-regulated and 22 down-regulated. However, there were 236 proteins altered only in nonNF1-CPT group, including 164 up-regulated and 72 down-regulated. The results indicated that the pathogenesis of NF1-CPT was similar as nonNF1-CPT largely with a few differences. Finally, compared with nonNF1-CPT, there were 47 proteins changed 1.5-fold and P-value <0.05 in NF1-CPT group. Conclusion:The proteins expression in the periosteum of CPT is different from that of normal tibia. The expression of periosteal protein is also different between NF1-CPT and nonNF1-CPT. The present study will deepen our understanding of the pathogenesis of CPT in the protein level.

Objective:To explore the safety of pamidronate disodium as adjuvant therapy in children with congenital pseudarthrosis of tibia (CPT).Methods:Medical record data of children with CPT who received pamidronate disodium for the first time and completed 3 doses of treatment during hospitalization in Department of Orthopedics, Hunan Children′s Hospital from July 1, 2019 to June 30, 2020 were collected and analyzed retrospectively. The regimen of medication was slow IV infusion of pamidronate disodium 0.5 mg/kg on day 1 and 1.0 mg/kg on days 2 and 3, dissolved in 0.9% sodium chloride injection 250 ml (the infusion time was >3 hours). Adverse reactions were monitored during and after the IV infusion. Peripheral venous blood was collected 2-3 hours after finishing the 3rd dose of treatment and blood calcium and phosphorus levels were detected. The children were divided into ≤1 year old group, >1-3 years old group, and >3 years old group, and the occurrence of adverse reactions in different age groups were compared.Results:A total of 81 children were enrolled in the analysis, including 54 males and 27 females, aged 0.4 to 15.4 years, with 10 cases in the ≤1 year old group, 46 in the >1 to 3 years old group, and 25 in the >3 years old group. After medication in the 81 children, fever with temperature ≥38.0 ℃ occurred 53 times in 34 children (42.0%), of which 39 times were grade 1 (38.0-39.0 ℃) and 14 times were grade 2 (>39.0-40.0 ℃). The incidence of fever on the day after the 2nd dose was significantly higher than that after the 1st and 3rd doses (all P<0.05). The differences in the incidence of fever and the degree of fever among the 3 groups were not statistically significant (all P>0.05). The temperature of children with fever decreased to below 38.0 ℃ within 1-16 hours after drug-therapy or physical cooling. After the 3rd dose of treatment, the levels of serum calcium and phosphorus were significantly lower than those before administration [(2.06±0.17) mmol/L vs. (2.42±0.12) mmol/L, (1.01±0.23)mmol/L vs. (1.71±0.18)mmol/L, all P<0.001]. The incidences of hypocalcemia and hypophosphatemia were 56.8% (46/81) and 19.8% (16/81) respectively, but none of patients with hypocalcemia and hypophosphatemia had obvious related symptoms. Conclusions:Pamidronate disodium is safe as adjunctive therapy in children with CPT. The main adverse reactions are fever, asymptomatic hypocalcemia, and hypophosphatemia. Fever can be recovered quickly after intervention, and the levels of serum calcium and phosphorus can return to within the normal range after drug withdrawal.

Objective:To explore the safety of pamidronate disodium as adjuvant therapy in children with congenital pseudarthrosis of tibia (CPT).Methods:Medical record data of children with CPT who received pamidronate disodium for the first time and completed 3 doses of treatment during hospitalization in Department of Orthopedics, Hunan Children′s Hospital from July 1, 2019 to June 30, 2020 were collected and analyzed retrospectively. The regimen of medication was slow IV infusion of pamidronate disodium 0.5 mg/kg on day 1 and 1.0 mg/kg on days 2 and 3, dissolved in 0.9% sodium chloride injection 250 ml (the infusion time was >3 hours). Adverse reactions were monitored during and after the IV infusion. Peripheral venous blood was collected 2-3 hours after finishing the 3rd dose of treatment and blood calcium and phosphorus levels were detected. The children were divided into ≤1 year old group, >1-3 years old group, and >3 years old group, and the occurrence of adverse reactions in different age groups were compared.Results:A total of 81 children were enrolled in the analysis, including 54 males and 27 females, aged 0.4 to 15.4 years, with 10 cases in the ≤1 year old group, 46 in the >1 to 3 years old group, and 25 in the >3 years old group. After medication in the 81 children, fever with temperature ≥38.0 ℃ occurred 53 times in 34 children (42.0%), of which 39 times were grade 1 (38.0-39.0 ℃) and 14 times were grade 2 (>39.0-40.0 ℃). The incidence of fever on the day after the 2nd dose was significantly higher than that after the 1st and 3rd doses (all P<0.05). The differences in the incidence of fever and the degree of fever among the 3 groups were not statistically significant (all P>0.05). The temperature of children with fever decreased to below 38.0 ℃ within 1-16 hours after drug-therapy or physical cooling. After the 3rd dose of treatment, the levels of serum calcium and phosphorus were significantly lower than those before administration [(2.06±0.17) mmol/L vs. (2.42±0.12) mmol/L, (1.01±0.23)mmol/L vs. (1.71±0.18)mmol/L, all P<0.001]. The incidences of hypocalcemia and hypophosphatemia were 56.8% (46/81) and 19.8% (16/81) respectively, but none of patients with hypocalcemia and hypophosphatemia had obvious related symptoms. Conclusions:Pamidronate disodium is safe as adjunctive therapy in children with CPT. The main adverse reactions are fever, asymptomatic hypocalcemia, and hypophosphatemia. Fever can be recovered quickly after intervention, and the levels of serum calcium and phosphorus can return to within the normal range after drug withdrawal.

OBJECTIVETo study in vitro anti-tumor activity of phaseoloideside E (PE) with human hepatoma HepG2 cells as the objective.

METHODMTT assay was adopted to detect the cytotoxic effect of PE of different concentrations on HepG2 cells after being processed for 48 h. Changes in morphology of PE-processed cells were observed under an optical microscope and fluorescence microscope. DNA agrose gel electrophoresis was used to detect the DNA ladder, an important characteristic of cell apoptosis. The expression levels of Bax and Bcl-2 were determined by western blot assay.

RESULTPE dramatically repressed the viability of HepG2 cells. Typical morphological changes of apoptosis had been detected by both direct microscopic observation and Hoechst 33,258 staining. Typical DNA Ladder was also observed by agarose gel electrophoresis in the administration group, but it did not exist in the control group. Western blot showed that the expression of Bax was up-regulated and Bcl-2 was down-regulated.

CONCLUSIONAbove data demonstrates that PE can induce apoptosis in human hepatoma HepG2 cells, and indicate that PE-induced expression level changes of Bax and Bcl2 may be related to the apoptosis-induction effect.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Saponins ; pharmacology ; Triterpenes ; pharmacology ; bcl-2-Associated X Protein ; analysis

OBJECTIVETo study the effect of total saponins from Entada phaseoloides (TSEP) on islet morphology and skeletal muscle PI3K pathway-related protein expression of type 2 diabetic rats.

METHODType 2 diabetic rats were induced by high-fat diet and low-dose streptozotocin and then randomly divided into 5 groups, i.e. the normal control, the model group, the positive control drug (200 mg x kg(-1) metformin), the low-dose TSEP (25 mg x kg(-1)) group and the high-dose TSEP (50 mg x kg(-1)). Three weeks later, the islet morphology of rat pancreas were observed by HE staining, and protein expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein tyrosine phosphatase-1B (PTP-1 B) and glucose transporter 4 (GLUT4) in rat skeletal muscle were detected by Western blot.

RESULTCompared with the modal group, TSEP administration groups showed relatively normal structures, clear pancreatic cells and intact capsula structures in pancreatic tissue pathological sections, with the number of pancreatic islets close to the normal control group. Meanwhile, above TSEP administration groups showed increased IRS-1, PI3K and GLUT4 protein expressions in their skeletal muscle tissues and decreased PTP-1B protein expression compared with the model group.

CONCLUSIONTSEP has an effect on protecting pancreatic tissues of type 2 diabetic rats and intervening in abnormal expression of proteins in skeletal muscle tissues.

Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; Fabaceae ; chemistry ; Glucose Transporter Type 4 ; analysis ; Islets of Langerhans ; drug effects ; pathology ; Male ; Muscle, Skeletal ; drug effects ; pathology ; Phosphatidylinositol 3-Kinases ; analysis ; Rats ; Rats, Sprague-Dawley ; Saponins ; therapeutic use