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@#Objective To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.
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OBJECTIVE@#The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment.@*METHODS@#Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ.@*RESULTS@#Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group.@*CONCLUSION@#EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.
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Rats , Male , Animals , Rats, Sprague-Dawley , Electroacupuncture , Proteomics , Cognitive Dysfunction/therapy , HippocampusABSTRACT
Objective:To study the genetic profiles and clinical characteristics of neonatal-onset genetic epilepsy.Methods:From July 2016 to May 2021, patients with neonatal-onset genetic epilepsy admitted to our hospital and received second-generation genetic sequencing were enrolled in this study. According to the types of genetic variations, the patients were assigned into ion channel group and non-ion channel group. Clinical characteristics, treatments and prognosis of the two groups were compared.Results:A total of 36 patients with identified genetic variations were enrolled, involving 15 epilepsy-related genes. KCNQ2, SCN2A and STXBP1 were the most common pathogenic genes. 20 cases (55.6%) were in the ion channel group and 16 cases (44.4%) in the non-ion channel group. No significant differences existed in their general status, seizure types, EEG characteristics, treatments and outcomes between the two groups ( P>0.05). Among all 36 cases, the age of onset ranged from 10 min to 24 d after birth and 28 cases (78.8%) developed epilepsy within 1 week after birth. Developmental and epileptic encephalopathies were diagnosed in 20 patients. 7 patients were diagnosed with self-limited neonatal epilepsy, 2 were pyridoxine dependence, 2 were Zellweger syndrome and 1 case of self-limited familial neonatal-infantile epilepsy, Turner type mental retardation with epilepsy, PURA syndrome, Rett syndrome and 22q11.2 deletion syndrome, each. The patients received antiepileptic drugs including phenobarbital, levetiracetam, oxcarbazepine, topiramate, valproic acid, benzodiazepines (nizepam/clonazepam /clobazam/midazolam), lacosamide and lamotrigine. 5 patients died after giving up treatment. 31 patients were followed up for 6 to 50 months. 22 cases (71.0%) were controlled at 1- to 35-month-old including 21 cases (56.7%) with developmental delay. 6 cases (19.4%) had ineffective seizure control and 3 cases (9.7%) showed reduced seizures, all with varying degrees of developmental delay. Conclusions:Neonatal-onset epilepsy is correlated with multiple genes. KCNQ2, SCN2A, STXBP1 are the common pathogenic genes with multiple variants of KCNQ2 gene. Most patients have seizures within 1 week after birth. More than half of patients have ion channel related gene variations. Sodium channel blockers have certain effects as treatment.
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Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.
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@#Objective To identify the preoperative risk factors for prolonged mechanical ventilation (PMV) after pulmonary thromboendarterectomy (PTE). Methods The clinical data of patients who underwent PTE from December 2016 to August 2021 in our hospital were retrospectively analyzed. The patients were divided into two groups according to the postoperative mechanical ventilation time, including a postoperative mechanical ventilation time≤48 h group (≤48 h group) and a postoperative mechanical ventilation time>48 h (PMV) group (>48 h group). Univariable and logistic regression analysis were used to identify the preoperative risk factors for postoperative PMV. Results Totally, 90 patients were enrolled in this study. There were 40 patients in the ≤48 h group, including 30 males and 10 females, with a mean age of 45.48±12.72 years, and there were 50 patients in the >48 h group, including 29 males and 21 females, with a mean age of 55.50±10.42 years. The results showed that in the ≤48 h group, the median postoperative ICU stay was 3.0 days, and the median postoperative hospital stay was 15.0 days; in the >48 h group, the median postoperative ICU stay was 7.0 days, and the median postoperative hospital stay was 20.0 days. The postoperative PMV was significantly correlated with tricuspid annular plane systolic excursion (TAPSE) [OR=0.839, 95%CI (0.716, 0.983), P=0.030], age [OR=1.082, 95%CI (1.034, 1.132), P=0.001] and pulmonary vascular resistance (PVR) [OR=1.001, 95%CI (1.000, 1.003), P=0.028]. Conclusion Age and PVR are the preoperative risk factors for PMV after PTE, and TAPSE is the preoperative protective factor for PMV after PTE.
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Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.
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Child , Humans , Male , Female , Exons , Glycogen Storage Disease/genetics , Hepatomegaly/genetics , Mutation , Phosphorylase Kinase/geneticsABSTRACT
Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation<moderate and peak trans-pulmonary pressure gradient<40 mmHg (1 mmHg=0.133 kPa). Results: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.
Subject(s)
Male , Humans , Pulmonary Valve/surgery , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation , Constriction, Pathologic/surgery , Prospective Studies , Ventricular Outflow Obstruction/surgery , Treatment Outcome , Cardiac Catheterization/methods , Transcatheter Aortic Valve ReplacementABSTRACT
Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation<moderate and peak trans-pulmonary pressure gradient<40 mmHg (1 mmHg=0.133 kPa). Results: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.
Subject(s)
Male , Humans , Pulmonary Valve/surgery , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation , Constriction, Pathologic/surgery , Prospective Studies , Ventricular Outflow Obstruction/surgery , Treatment Outcome , Cardiac Catheterization/methods , Transcatheter Aortic Valve ReplacementABSTRACT
OBJECTIVES@#To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.@*METHODS@#A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed.@*RESULTS@#The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05).@*CONCLUSIONS@#Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.
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Child , Humans , Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Familial Hypophosphatemic Rickets/diagnosis , Rickets, Hypophosphatemic/diagnosisABSTRACT
Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na+-K+-2Cl-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type Ⅰ.
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Child, Preschool , Female , Humans , Infant , Male , Pregnancy , Bartter Syndrome/genetics , HEK293 Cells , Homozygote , Retrospective Studies , Solute Carrier Family 12, Member 1/geneticsABSTRACT
Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.
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OBJECTIVE@#To analyze the clinical characteristics and prognosis of 40 children with myelodysplastic syndrome (MDS), and provide ideas for clinical diagnosis and treatment.@*METHODS@#The clinical characteristics, risk stratification, and different treatment regimens of 40 cases with MDS admitted in Department of Hematology of Children's Hospital of Soochow University from January 1, 2011 to December 31, 2017 was retrospectively analyzed. Kaplan-Meier survival curve were used to estimate 3-year overall survival (OS) rate and event-free survival (EFS) rate.@*RESULTS@#In 40 cases, the ratio of male to female was 1.4∶1.0, male was more than female, and median age was 6.0 years old. Among them, refractory cytopenia (MDS-RCC) was the most common type, and 11 cases were chromosomal abnormalities, 21 cases genetic abnormalities. Fifteen cases accepted hematopoietic stem cell transplantation (HSCT) treatment, while 25 cases did not but drug therapy alone. The 3-year OS rate of the cases who accepted HSCT or not was (72.2±12.2)% and (35.3±10.2)% (P=0.039), 3-year EFS rate was (65.0±12.9)% and (19.2±8.4)% (P=0.012), respectively. Cox regression analysis showed that age < 7 years old (P=0.0333), initial diagnosed platelet < 50×109/L (P=0.007), presence of complex karyotypes and/or gene mutations (P=0.0002), and treatment without HSCT (P=0.016) were the high-risk factors of prognosis. All the children were classified according to IPSS, WPSS and IPSS-R, while analysis result showed that the above three risk assessment had limitations for risk assessment of MDS in children, they could not comprehensively assess the prognosis of children with MDS.@*CONCLUSION@#MDS-RCC in children is more common. Cox multivariate analysis shows that age < 7 years old, initial diagnosed platelet < 50×109/L, presence of complex karyotypes and/or gene mutation, and treatment without HSCT are the high-risk factors of prognosis in children with MDS. HSCT is the most effective treatment to cure children with MDS at present. The current methods such as IPSS-R commonly used in assessment of prognosis in children with MDS show obvious limitation.
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Child , Female , Humans , Male , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes/therapy , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
Objective To investigate the relationship between the G894T polymorphism of the endothelial nitric oxide synthase (eNOS) gene and the lipid metabolism in patients with irypertensive disorder complicating pregnancy (HDCP). Methods The 528 cases of HDCP patients admitted to the Xingtai Third Hospital from January 2016 to January 2020 were selected as the research objects, and 128 normal pregnant women during the same period were selected as the control group. The fasting peripheral venous blood of all stud)' subjects in the early morning was collected, and blood lipid indexes, cystatin C (CysC) and uric acid levels and other biochemical index levels were measured. According to the blood lipid level, it was divided into normal blood lipid group and dyslipidemia group. The dyslipidemia group included 4 subgroups [ hyper triglyceride (TG) blood group (T G
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Objective To observe the anatomical structure of spinoglenoid notch of scapula by 3D reconstruction of normal adult scapula by computed tomography (CT), and to provide reference for clinical assessment of suprascapular nerve compression risk, suprascapular nerve compression treatment and shoulder joint operation. Methods Totally 335 cases of normal adult scapula were reconstructed by CT, and classified according to the anatomical shape of spinoglenoid notch; the spinoglenoid notch width (MN), spinoglenoid notch depth (OP), spinoglenoid notch thickness (XY), spinoglenoid notch angle (Z.M0N), distance from 0 point to the inner upper corner of scapula (0A), distance from 0 point to medial lateral edge of scapula (OB), distance from 0 point to inferior angle of scapula (OC) and distance from 0 point to the lowest point of suprascapular notch (OD) were observed and analyzed. Results 1. The morphology of spinoglenoid notch was divided into four types; U type (41. 79%), fin type (42. 99%), L type (8. 36%) and ladder type (6. 86%). U type and fin type were the most common types. Comparison of the four shapes; fin type was the narrowest (11.58 ± 1.74) mm and the deepest (14.58 ± 1.81) mm, the /_ M0N was the smallest (45.62 ± 6.43) ° and the ladder type was the widest (14. 20 ± 2. 67) mm and the shallowest (10. 80 ± 0. 79) mm, the Z.MON was maximum (57. 69 ± 2. 22) ° and the least prone to suprascapular nerve compression. 2. There was no significant difference in MN, OP, XY, zlMON, OA, OB, 0C and OD between left and right sides. 3. The data of MN, OP, XY, OA, OB, OC and OD of men were larger than those of women significantly, but Z. MON was smaller than that of women, indicating that men' s spinoglenoid notch was thicker, wider and deeper, and scapula was wider and longer than that of women. Conclusion The measurement of the morphological and anatomical characteristics of spinoglenoid notch with CT three-dimensional reconstruction is helpful to evaluate the risk of suprascapular nerve compression, the treatment of suprascapular nerve compression, and provide guidance for clinical shoulder surgery.
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Objective:To explore the effect of Duanteng Yimu decoction (DTYM) on the activation of the human umbilical vein endothelial cell (HUVEC) model and the effect on related activated proteins and vascular endothelial growth factor (VEGF) signaling pathway. Method:After DTYM (200, 400 g·mL<sup>-1</sup>) treatment of HUVEC induced by VEGF and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), cell proliferation, migration, and tubulogenesis were detected by cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell migration assay, phalloidin staining, and matrix gel card method. The mRNA expression of adhesion factors, including E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of von Willebrand factor (VWF), platelet-endothelial cell adhesion molecule-31 (CD31), angiogenic factor cysteine-rich-61 (CYR61), angiopoietin-1 (ANG-1), VEGF, and VEGF receptor-2 (VEGFR2) was detected by Western blot. Immunofluorescence was used to determine CD31 expression. Result:Compared with the normal group, the model group showed potentiated proliferation, migration, and tubulogenesis of HUVEC (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated mRNA expression of E-selectin, ICAM-1, and VCAM-1 (<italic>P</italic><0.01), up-regulated protein expression of VWF, CD31, ANG-1, CYR61, VEGF-<italic>α</italic>, and phospho (p)-VEGFR2 (<italic>P</italic><0.05,<italic> P</italic><0.01), and increased CD31 immunofluorescence intensity (<italic>P</italic><0.01). Compared with the model group, the DTYM groups displayed blunted proliferation, migration, and tubulogenesis of HUVEC (<italic>P</italic><0.05,<italic> P</italic><0.01), decreased mRNA expression of E-selectin, ICAM-1, and VCAM-1 (<italic>P</italic><0.05, <italic>P</italic><0.01), down-regulated protein expression of VWF, CD31, ANG-1, CYR61, VEGF-<italic>α</italic>, and p-VEGFR2 (<italic>P</italic><0.05, <italic>P</italic><0.01), and weakened CD31 immunofluorescence intensity (<italic>P</italic><0.01). Conclusion:DTYM inhibits HUVEC proliferation, migration, adhesion, and tubulogenesis, which is associated with the regulation of CD31, VWF, CYR61, and ANG-1 expression in HUVEC and the VEGF signaling pathway.
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Objective:To investigate the mechanism of Duanteng Yimu decoction (DTYM) in the inhibition of pannus formation in collagen-induced arthritis (CIA) mice. Method:Twenty-four SPF-grade DBA/1 male mice were randomly divided into the following four groups: a blank group (NC group), a model group (CIA group), a methotrexate group (MTX group), and a DTYM group, with six mice in each group. The mice, except for those in the NC group, were modeled. From the second immunization, the medium, MTX (1 mg·kg<sup>-1</sup>), and DTYM (15.4 g·kg<sup>-1</sup>) were administered at an equal volume by gavage for 35 days. Mice were observed for general condition and the arthritis index. The knee and ankle joints were scanned by microcomputed tomography (micro CT). Hematoxylin-eosin (HE) and safranin O/fast green staining were performed to observe pathological changes. Immunohistochemistry was performed to detect the expression of platelet/endothelial cell adhesion molecule-1 (CD31), vascular endothelial growth factor-<italic>α</italic> (VEGF-<italic>α</italic>), vascular endothelial growth factor receptor 2 (VEGFR2), and phosphorylated(p)-VEGFR2. Result:Compared with the NC group, the CIA group showed red and swollen ankle joints, increased arthritis index scores (<italic>P</italic><0.05, <italic>P</italic><0.01), manifest injury in the knee and ankle joints, reduced cartilage thickness, elevated Micro CT bone destruction scores of knee and ankle joints (<italic>P</italic><0.01), and up-regulated absorbance values of synovial CD31, VEGF-<italic>α</italic>, VEGFR2, and p-VEGFR2 (<italic>P</italic><0.01). Compared with the CIA group, the DTYM group showed relieved ankle joint redness and swelling, reduced arthritis index scores of mice three weeks after administration (<italic>P</italic><0.05, <italic>P</italic><0.01), intact joint surfaces of the knee and ankle joints, thickened cartilage, declining Micro CT bone destruction scores in both the knee and ankle joints (<italic>P</italic><0.05, <italic>P</italic><0.01), and lowered absorbance values of CD31, VEGF-<italic>α</italic>, VEGFR2, and p-VEGFR2 in the synovium (<italic>P</italic><0.01). Conclusion:DTYM can inhibit the pannus formation in CIA mice presumedly by regulating the VEGF pathway.
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Objective:To analyze the diagnosis, treatment, and outcomes of neonates with deep venous thrombosis (DVT) of the extremities and torso.Methods:The clinical diagnosis, treatment and outcomes of seven neonates with DVT of the extremities and torso admitted to Beijing Children's Hospital, Capital Medical University from March 2016 to March 2020 were retrospectively analyzed. Paired t test and paired rank sum test were used to compare the difference of coagulation indexes before and after the anticoagulant therapy. Results:Among the seven neonates with DVT of the extremities and torso, six were male and five were term infants, with the gestational age of (37.9±2.5) weeks and birth weight of (2 989±619) g. The median age at admission was 2.0 d and the age at diagnosis was 3.0 d. Except for one case of left common femoral vein thrombosis with limb swelling on the affected side, the other cases were all found with DVT by routine abdominal ultrasound examination after admission. Six cases received heparin treatment with the median duration of 8.5 d (1.8-28.8 d), including four cases of thrombosis in the portal venous, one in the postcava and renal venous, and one in the left common femoral vein. Among the six cases, the thrombus disappeared in five cases, which were confirmed by vascular ultrasound examination during follow-up, and in another case, the thrombus was shrinked significantly but remained. After the treatment, the platelet count [(464.5±128.9)×10 9/L vs (142.5±104.2)×10 9/L, t=-5.019, P=0.004] and antithrombin-Ⅲ level [(67.08±28.87)% vs (46.05±12.60)%, Z=-2.201, P=0.028] were increased and the D-dimers was decreased [0.392 mg/L(0.250-0.884 mg/L) vs 2.511 mg/L(0.755-14.033 mg/L), Z=-2.201, P=0.028] with no reports of heparin-related side-effect. One case with advanced postcaval thrombosis did not receive heparin anticoagulant therapy, but the thrombosis disappeared 270 d after diagnosis during follow-up. Conclusions:DVT of the extremities and torso may have no specific symptoms during the neonatal period and the overall prognosis is good. Heparin anticoagulant therapy is recommended until thrombosis disappears for patients with large thrombosis or significantly high level of D-dimer. The course of heparin treatment varies greatly among individuals, and close monitoring is required.
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OBJECTIVE@#To explore the mechanism by which ginsenoside 20(S)-Rg3 upregulates the expression of tumor suppressor von Hippel-Lindau (VHL) gene in ovarian cancer cells.@*METHODS@#Ovarian cancer cell line SKOV3 treated with 20(S)-Rg3 were examined for mRNA and protein levels of VHL, DNMT1, DNMT3A and DNMT3B by real-time PCR and Western blotting, respectively. The changes in VHL mRNA expression in SKOV3 cells in response to treatment with 5-Aza-CdR, a DNA methyltransferase inhibitor, were detected using real-time PCR. VHL gene promoter methylation was examined with methylation-specific PCR and VHL expression levels were determined with real-time PCR and Western blotting in non-treated or 20(S)-Rg3-treated SKOV3 cells and in 20(S)-Rg3-treated DNMT3A-overexpressing SKOV3 cells. VHL and DNMT3A protein levels were detected by immunohistochemistry in subcutaneous SKOV3 cell xenografts in nude mice.@*RESULTS@#Treatment of SKOV3 cells with 20(S)-Rg3 significantly upregulated VHL and downregulated DNMT3A expressions at both the mRNA and protein levels (@*CONCLUSIONS@#Ginsenoside 20(S)-Rg3 upregulates VHL expression in ovarian cancer cells by suppressing DNMT3A-mediated DNA methylation.
Subject(s)
Animals , Female , Humans , Mice , Cell Line, Tumor , DNA Methylation , Gene Expression , Ginsenosides/pharmacology , Mice, Nude , Ovarian Neoplasms/genetics , Promoter Regions, Genetic , Von Hippel-Lindau Tumor Suppressor Protein/geneticsABSTRACT
Immunotherapy, especially immune checkpoint inhibitors (ICIs), has reformed the situation of cancer management. Encouraging results have been revealed in early stage studies about ICIs in patients with hepatocellular carcinoma.Results of a recent phase Ⅲ study of ICIs combined with anti-angiogenesis therapy in the treatment of hepatocellular carcinoma have achieved a positive result, showing superior advantages in efficacy and safety compared with standard manage-ment. At present, lots of studies in hepatocellular carcinoma patients treated with ICIs combining with traditional therapy like chemotherapy, radiotherapy, antiangiogenetic therapy, locore-gional therapy and another ICIs are held globally. These results will update the strategies of hepatocellular carcinoma.
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OBJECTIVE@#To investigate the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and deterioration of global and specific domains of cognitive function in peritoneal dialysis (PD) patients.@*METHODS@#This was a multi-center prospective cohort study. The PD patients who met the inclusion criteria were examined with general and specific cognitive function between March 2013 and November 2013. The patients were divided into MIA0, MIA1 and MIA2 groups, according to items of "Yes" for whether or not having cardiovascular disease, serum albumin≤35 g/L or high-sensitive C-reactive protein (hs-CRP) ≥3 mg/L. After 2 years, the patients maintained on PD would be repeatedly measured with cognitive function. The Chi-square test, One-way ANOVA, Kruskal-wallis H rank sum test were used to compare the differences of clinical characteristics, biochemical data, and global and specific cognitive function parameters among the three groups at baseline, and two years later, respectively. The Bonferroni method was applied to adjust the significance level for further comparison between each two different groups. The change of score in each cognitive parameter of global and specific domains was used as dependent variable. Age, gender, education level, depression index, body-mass index, diabetes mellitus, serum sodium levels and MIA (MIA0 was control, MIA1 and MIA2 as dummy variables) were all included in the multivariable linear regression models to analyze the risk factors of the deterioration of cognitive function. The analysis for each cognitive domain was adjusted for the baseline score of the corresponding cognitive parameter. All the analyses were performed using SPSS for Windows, software version 25.0 (SPSS Inc., Chicago, IL).@*RESULTS@#Over two-year follow up, the prevalence of cognitive impairment increased from 20.0% to 24.7%, absolute decrease of 3MS scores were more significantly decreased in MIA2 (-3.9±12.0 vs. 1.1±6.7, P<0.01) and MIA1 group (-2.3±11.8 vs. 1.1±6.7, P<0.05) than those in MIA0 group respectively. Specific cognitive functions, included executive function (trail-making tests A and B, P=0.401, P=0.176), immediate memory (P=0.437), delayed memory (P=0.104), visuospatial skill (P=0.496), and language ability (P=0.171) remained unchanged. Advanced age, lower education, diabetes mellitus and depression were all correlated with the deterioration of one or more cognitive domains, and the patients having one item of MIA syndrome were prone to develop the deterioration of 3MS (P=0.022). Furthermore, the patients having two or more items of MIA syndrome were more likely to develop the deterioration of not only 3MS (P <0.001), but also delayed memory, visuospatial skill, and language ability (P=0.002, P=0.007, P=0.004, respectively).@*CONCLUSION@#Patients with one item or above of MIA syndrome were at high-risk for the deterioration of global cognitive function. The more MIA syndrome items there were, the more specific cognitive domains deteriorated.