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Abstract@#With the increasing prevalence of overweight and obesity in children, the influence of overweight and obesity on pubertal timing has attracted the attention of scholars. This paper reviewed the correlation and mechanism between childhood obesity and pubertal timing, especially for earlier pubertal timing, and found that the regulation of hypothalamic-pituitary-gonadal axis function by nutrition and metabolic signals might under lie those associations. Obesity in girls was positively correlated with early pubertal timing, while the conclusions in boys were inconsistent. Overweight in boys was related to early pubertal timing, obesity in boys could lead to both earlier and later onset of puberty, which warrents further investigation.
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Stroke has become a major health issue worldwide, bringing a heavy burden to patients, families, and society. Effective reperfusion therapy can significantly improve the outcomes of patients with acute ischemic stroke (AIS). The secondary prevention guidelines in various countries recommend reducing stroke risk by strictly controlling blood pressure. With the widespread application of 24-hour ambulatory blood pressure monitoring, the study of blood pressure variability (BPV) has gradually become a hot topic in the field of stroke prevention and treatment. However, the impact of BPV on the outcomes of patients with AIS receiving reperfusion therapy remains controversial. This article mainly reviews the concept and the related parameters of BPV, as well as the relationship and possible mechanisms between BPV and the outcomes of patients with AIS receiving reperfusion therapy.
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Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.
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Child , Infant, Newborn , Humans , Infant , Pulmonary Atresia/surgery , Ductus Arteriosus , Retrospective Studies , China , Heart Defects, Congenital , Ductus Arteriosus, Patent/surgery , Heart Septal Defects, Ventricular , StentsABSTRACT
Non-small cell lung cancer (NSCLC) is one of the most severe malignant tumors worldwide. Lobectomy and systematic nodal dissection remain the standard treatment for stageⅠNSCLC. Stereotactic body radiotherapy (SBRT) has become the standard treatment for medically inoperable patients. Though the prognosis of stage Ⅰ NSCLC patients is generally good, there are still about 20% of patients with local recurrence and distant metastasis. There is significant heterogeneity in the prognosis and failure phenotype of patients, which cannot be precisely distinguished by the pathological TNM classification system. Identification of the risk factors for the prognosis of patients with stage Ⅰ NSCLC is a key step to realize the treatment from experience to precision. Screening the high-risk patients will facilitate to individually develop the adjuvant therapy strategy after surgery or SBRT and improve the overall curative effect. There are many factors that are significantly related to the prognosis of stage Ⅰ NSCLC including individual factors such as gender, age, and systemic inflammatory biomarkers; treatment-related factors such as the extent of surgical resection of the primary tumor and lymph nodes, the choice of different radiation rays, and different dose fractionation; and tumor-related factors such as imaging information, pathology information; and molecular biology information. This review will analyze the treatment failure phenotype and prognostic factors of stageⅠ NSCLC in various perspectives such as individual-, tumor- and treatment-related factors.
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Humans , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/pathology , Phenotype , Prognosis , Treatment FailureABSTRACT
Multiple sclerosis ( MS) is an immune-mediated chro¬nic inflammatory disease of the central nervous system (CNS) , which is regulated by multiple pathophysiological mechanisms.There are four clinical phenotypes of MS, including relapsing-re- mitting MS ( RRMS) , primary progressive MS ( PPMS) , sec- ondary-pmgressive MS ( SPMS) , and progressive relapsing MS ( PRMS) , among which RRMS is the main type.'Hie pathogen¬esis of MS is not clear and it could not he cured, so long-term drug treatment is needed for the MS patients.Nowadays, animal models play an important role in the preclinical research of MS drugs.'Hie MS animal models are mainly divided into experi¬mental autoimmune encephalomyelitis (EAE) model, toxin in¬ duced demyelination model, and vims induced demyelination model, among which EAE model is most widely used.'Hie three types of MS animal models demonstrate specific characteristics due to the different induction methods and animal species, and they correspond to specific clinical types of MS.According to the different clinical types of MS, the use of appropriate animal models for drug research and development will help us develop more targeted and potential therapeutic dnrgs, making it possible to cure MS.
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Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.
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@#BACKGROUND: Sepsis-induced liver injury is a fatal complication of sepsis. Trichostatin A (TSA) regulates inflammation and autophagy in some human diseases, and forkhead box O3a (FoxO3a) has been shown to regulate autophagy. The present study aims to investigate whether TSA exerts its effects on septic liver injury through the FoxO3a/autophagy signaling pathway. METHODS: A sepsis mouse model was constructed by the cecal ligation and puncture (CLP) method, and AML12 cells were pretreated with lipopolysaccharide (LPS) (1 μg/mL) to establish a sepsis cell model. Forty mice were divided into four groups, namely control group, TSA group, CLP group, and CLP+TSA group, with 10 mice in each group. Cells were divided into control group, TSA group, LPS group, and LPS+TSA group. Hematoxylin-eosin (H&E) staining and biochemical methods were used to evaluate liver tissue injury. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of proinflammatory cytokines, and Western blotting and immunofluorescence were used to measure autophagy-related protein expression. RESULTS: Compared with the CLP group (mice), the proinflammatory cytokines (interleukin-β [IL-β] 2,665.27±324.90 pg/mL to 2,080.26±373.66 pg/mL; interleukin-6 [IL-6] 399.01±60.98 pg/mL to 221.90±46.89 pg/mL) and the hepatocyte injury markers (aspartate transaminase [AST] from 198.18±27.07 U/L to 128.42±20.55 U/L; alanine aminotransferase [ALT] from 634.98±74.10 U/L to 478.60±32.56 U/L) were notably decreased after TSA intervention. Moreover, LC3 II and FoxO3a showed an obvious increase and P62 showed an obvious decrease in the CLP+TSA group. Cell experiment results showed the similar trend. After FoxO3a gene was knocked down in AML12 cells, the promotion of autophagy and the improvement of liver enzyme index and inflammation by TSA were weakened. CONCLUSION: TSA may improve the inflammatory response and liver injury in septic mice through FoxO3a/autophagy.
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Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations and complex pathogenesis, characterized by loss of immune tolerance to autoantigens and production of large amounts of autoantibodies. Interferon (I F N) signaling pathway is one of the pathogenetic pathways widely recognized at present. In recent years, the correlation between IFN signaling and epigenetic modification in the occurrence and development of SLE has beena research hotspot. And in this paper, the relevant studies are reviewed in order to provide new research ideas for the pathogenesis of SLE.
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Diabetes and heart failure (HF) are common diseases, each affecting large segments of the world population. Moreover, prevalence rates for both are expected to rise dramatically over coming decades. The high prevalence rates of both diseases and wellrecognized association of diabetes as a risk factor for HF make it inevitable that both diseases co-exist in a large number of patients, complicating their management and increasing the risk of a poor outcome. Management of diabetes has been shown to impact clinical events in patients with HF and there is emerging evidence that agents used to treat diabetes can reduce HF events, even in non-diabetic patients. In this review we summarize the clinical course and treatment of patients with type 2 diabetes mellitus (T2DM) and HF and review the efficacy and safety of pharmacological agents in patients with T2DM at risk for HF and those with established disease.
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Objective:To explore a new method of ultrasound-guided positioning of the tip of neonatal peri-pherally inserted central catheter (PICC).Methods:Clinical data of 174 newborn infants hospitalized in the Neonatal Intensive Care Unit (NICU) of Beijing Chaoyang District Maternal and Child Healthcare Hospital from January 2019 to April 2021 receiving PICC catheter intubated under the guidance of ultrasound for positioning the tip were retrospectively analyzed to explore the accuracy, reliability and feasibility of the improved ultrasound-guided positioning technique.Before lower extremity catheterization, ultrasound was performed to monitor the vascular pattern and catheterization of PICC was conducted under the guidance of ultrasound.Results:(1) Among 174 infants intubated with ultrasound-guided positioning of the PICC tip, 172(98.9%) of them had the ideal position, and 2(1.1%) did not achieve the ideal position, but achieved the ideal position after ultrasound-guided correction.(2) Lower extremity venous catheterization was successfully performed at 100.0% after ultrasound-guided monitoring of blood vessels.The time-consuming of lower extremity venous catheterization was significantly shorter than that of the previous method [(31.50±2.58) min vs.(56.10 ±5.30 min)]( t=46.84, P<0.001). The total success rate of catheterization and catheterization of lower limb vein increased by 7.0% and 17.5%, respectively.(3) Only 1 (0.57%) case reported the complication of catheter tip thrombosis, the complication rate of which decreased from the previous 79.00% to 2.70%(2/112 cases). Conclusions:The improved ultrasound-guided positioning of the PICC tip is convenient, simple, faster and accurate, which enhances the success rate and is worthy to be applied in clinical practice.
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Diabetes and heart failure (HF) are common diseases, each affecting large segments of the world population. Moreover, prevalence rates for both are expected to rise dramatically over coming decades. The high prevalence rates of both diseases and wellrecognized association of diabetes as a risk factor for HF make it inevitable that both diseases co-exist in a large number of patients, complicating their management and increasing the risk of a poor outcome. Management of diabetes has been shown to impact clinical events in patients with HF and there is emerging evidence that agents used to treat diabetes can reduce HF events, even in non-diabetic patients. In this review we summarize the clinical course and treatment of patients with type 2 diabetes mellitus (T2DM) and HF and review the efficacy and safety of pharmacological agents in patients with T2DM at risk for HF and those with established disease.
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BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,
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Ischemic stroke is one of the leading causes of death and disability worldwide. A large number of preclinical studies have demonstrated that exogenous cell-based therapies such as mesenchymal stem cell transplantation can promote brain function recovery in the subacute phase of stroke. Emerging data indicate that mesenchymal stem cell-derived exosomes play a key role in mediating tissue repair by participating in intercellular signal transduction and transferring biological information especially microRNA to recipient cells, which affects endo-genous recovery in ischemic brain tissue after injury. In this review we briefly describe the characteristics and biological functions of exosomes and exosomal microRNA, and discuss the therapeutic effects of mesenchymal stem cell-derived exosomes on ischemic stroke from different perspectives. Finally, we outline the potential clinical value of exosomes and challenges of translating these therapies into clinical trials.
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@#To assess the relationship between high blood pressure (HBP) and body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR) among children and adolescents in Suzhou.@*Methods@#A total of 3 150 children and adolescents aged 7-17 years were enrolled through stratified cluster sampling from September to October, 2019. Questionnaire survey was conducted, and height, weight, WC and BP were measured to calculate BMI and WHtR, relationship of HBP and adiposity indicators were evaluated.@*Results@#The prevalence of HBP was 11.3%, overweight/obesity rate was 28.5%, and centrality obesity based on WC and WHtR was 20.6% and 23.7%, respectively. There were significant relationships between HBP and BMI, WC, and WHtR (χ2=157.80,105.87,124.17,P<0.01). As Logistic regression showed, compared to normal weight group, overweight/obesity based on BMI had positive relation with HBP (OR=3.89, 95%CI=3.09-4.90); compared to normal WC/WHtR, centrality obesity showed positive association with HBP (WC: OR=3.05, 95%CI=2.41-3.86; WHtR: OR=3.35, 95%CI=2.67-4.21). Meanwhile, BMI had joint effects on HBP with WC/WHtR. Specifically subjects with overweight/obesity and center obesity had higher risk of HBP, compared to normal BMI and WC subjects(OR=4.28, 95%CI=3.31-5.53).@*Conclusion@#Significant relationships between HBP and BMI, WC, and WHtR were found. BMI had joint effects on HBP with WC/WHtR. Keeping normal body weight and WC/ WHtR would have significant effects on HBP.
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Objective@#To investigate the value of ultrasound in the localization of peripherally inserted central catheter (PICC) in neonates.@*Methods@#A retrospective analysis of the PICC catheterization was conducted at Department of Neonatology, Beijing Chaoyang District Maternal and Child Healthcare Hospital from June 2017 to December 2018.The ultrasound monitoring was performed immediately after PICC catheterization.The probe was placed into the midline position of the lower xiphoid or the subclavian parasternal line for scanning, and it would be the PICC if a high-echo " equal sign" was observed by ultrasound.It was believed that the PICC was successfully placed when ultrasound detected that the PICC tip was located in the junction of inferior vena cava or superior vena cava in the right atrium.@*Results@#(1)Among 112 infants with PICC catheterization, 103 cases (92.0%) were accurately placed, 9 cases (8.0%) were not placed in the ideal site, among them, 2 cases were too deep, 4 cases were too shallow and 3 cases were catheter heterotopia.The tip position was accurate after the readjustment under ultrasound monitoring in those patients whose the first ultrasound showed the tip position was not ideal.(2)The PICC indwelling time was as short as 2 days (removed due to severe arrhythmia) and as long as 56 days with an average of (15.1±10.7) days.(3)The catheter-related complications occurred in 3 cases with an incidence of 2.7%.@*Conclusions@#Using ultrasound to determine the PICC tips position is accurate and reliable, which is worthy of extensive application in the neonatal wards.
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OBJECTIVE@#To observe the clinical effect of six-step manipulation combined with extracorporeal shock wave in the treatment of knee osteoarthritis.@*METHODS@#Seventy-six patients with KOA from December 2016 to June 2018 were divided into control group and treatment group, 38 in each group. The patients in the control group were treated with oral medicine combined with extracorporeal shock wave therapy, while the patients in the treatment group were treated with six-step manipulation combined with shock wave therapy. The VAS score, WOMAC score and clinical efficacy of the two groups were compared before treatment, 1 day, 1 month and 6 months after treatment.@*RESULTS@#There was no significant difference in VAS score and WOMAC score between the two groups before treatment(>0.05). VAS score and WOMAC score in treatment group were significantly lower than those in control group at 1 day, 1 month and 6 months after treatment, and the difference was statistically significant(<0.05).@*CONCLUSIONS@#Six-step manipulation combined with extracorporeal shock wave therapy can significantly alleviate pain and improve knee function in patients with knee osteoarthritis, and the clinical effect is obvious.
Subject(s)
Humans , Acupuncture Therapy , Extracorporeal Shockwave Therapy , Knee Joint , Osteoarthritis, Knee , Therapeutics , Treatment OutcomeABSTRACT
Objective The aim of current study was to evaluate the effect of growth differentiation factor 15( GDF-15) on predicting and monitoring the cardiotoxicity of epirubicin/cyclophosphamide-docetaxel-trastuzumab(EC-D-T)in the treatment of HER-2 positive breast cancer patients. Methods Seventy-three patients with HER-2 positive breast cancer who received EC-D-T adjuvant therapy were enrolled. Serum levels of GDF-15,cardiac troponin I(cTnl)and amino terminal brain natriuretic peptide precursor(NT-proBNP)were measured before adjuvant therapy(M0)and after adjuvant therapy at 3 months(M3 ),6 months(M6 ),9 months(M9 ),12 months(M12 )and 15 months(M15 ). At the same time,patients underwent echocardiography at various time points to assess the left ventricular ejection fraction(LVEF). The cardiotoxicity of this study was defined as:(1)LVEF level decreased by ≥10% after treatment and the absolute value of LVEF was below 53% (normal);(2) heart failure,acute coronary syndrome or severe life-threatening heart rate abnormal. Results After initiation of EC-D-T treatment,the level of LVEF gradually decreased. Dur-ing the whole study,a total of 21(28. 8% )patients developed cardiotoxicity. At the same time,patients with cardiotoxicity had signifi-cantly higher levels of GDF-15 at M0 and cTn1 at various time points than those without cardiotoxicity. The level of ProBNP was comparable to those without cardiotoxicity. In addition,Univariate logistic regression analysis showed that baseline GDF-15 might af-fect the risk of cardiotoxicity. Multivariate logistic regression analysis showed that only cTnl level was an independent predictor for the risk of cardiotoxicity, while NT-proBNP level did not predict the risk of cardiotoxicity. Conclusion The incidence of cardiotoxicity in patients with HER-2 positive breast cancer after receiving EC-D-T is high,and GDF-15 can predict and monitor the risk of cardiotoxicity.
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Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease,and a large number of eosinophils (EOS) obviously infiltrate the dermis of BP lesions.Additionally,EOS and their activated cytokines and chemokines are abundantly present in blisters and peripheral blood of BP patients.It is also proved that EOS can induce the dermal-epidermal separation.The level of interleukin (IL)-5 is markedly increased in the sera and blister fluids of BP patients,and IL-5 secreted by Th2 cells and EOS can regulate the differentiation,activation and survival of EOS.All the above evidence indicates that EOS are associated with the occurrence of BP.Researches on EOS and their cytokines will develop a new field of targeted therapy for BP.
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Objective To compare the clinical outcomes of low-dose rabbit antithymocyte globulin (rATG ) vs basiliximab as induction therapy in recipients of ABO-incompatible kidney transplantation (ABOi-KT) .Methods Retrospective analysis was conducted for e the clinical data of 40 ABOi-KT recipients between March 2017 and March 2019 .17 recipients of them received induction therapy with basiliximab (basiliximab group) while another 23 recipients received low-dose rATG (rATG group ,rATG 25 mg/d × 3 d) .During a median follow-up period of 282 days , the data of serum creatinine and eGFR at 1 week and 1 month ,graft survival rate and complication rate of two groups were compared .Results No significant difference existed in age ,gender ,dialytic modality/ duration , blood groups of recipients , HLA mis-match , blood group antibody titers , dose of rituximab ,blood groups of donors or donor age ( P > 0 .05 ) . The times of double filtration plasmapheresis in Basiliximab group were more (P< 0 .05) .No significant difference existed in serum creatinine and eGFR at 1 week or 1 month ( P > 0 .05 ) . No significant difference existed in graft survival rate . No significant difference existed in rate of acute rejection ,parvovirus B19 infection , urinary tract infection or hematoma .Conclusions Low-dose of rATG is as effective as basiliximab for ABOi-KT recipients .And rATG does not increase the rate of infection .
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Gold nanoclusters (AuNCs) are gold atom aggregates less than 2 nm (excluding the ligand shell) or 150 atoms. It has been widely studied due to its small size effect, fluorescence property, and catalytic activity. In this review, research progress in the preparation of gold nanoclusters containing accurate atom numbers using biomolecules and chemically synthesized molecules as ligands have been summarized. The factors that affect the preparation of gold nanoclusters have been discussed. The applications of AuNCs having accurate atomic numbers in the fields of analyte assay, catalysis, bioimaging, and drug delivery have been introduced. This review provides references to the further researches on the preparation technology and biomedical applications of AuNCs.