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Background: Hypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?, Objective: We aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults., Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014-2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship., Results: During a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs  < 35g/L [HR: 1.33 (95%CI, 1.10, 1.62)] and CI vs normal cognition [HR: 1.69 (95%CI, 1.43, 1.99)] independently predicted mortality. A dose-response relationship with mortality was observed for albumin quartiles ( p  < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased the mortality risk by 155%, with a notably higher risk in males, those aged <85 years, and individuals living in rural areas. Interaction effects of albumin and CI on mortality were observed ( p  < 0.001). In the single CI group, older adults had a 61% increased risk of mortality in the hypoproteinaemia group compared with the albumin-normal group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk., Conclusion: Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects observed in males, younger older adults, and those living in rural areas. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liu, Wang, Shen, Cao, Guan, Zhang and Liu.)

Objectives: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence., Methods: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed., Results: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group ( P >0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage ( n =62, 42.5%) and the early stage ( n =46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene ( HR =4.177, 95% CI : 2.086-8.364, P <0.001) and minimal residual disease≥0.01% on day 46 ( HR =2.013, 95% CI : 1.163-3.483, P =0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol., Conclusions: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA)., Methods: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated., Results: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference ( P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor ( P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×10 9 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST ( P =0.020, OR =0.062), and high PLT count was a protective factor ( P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence ( P =0.001, 0.031)., Conclusion: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.

Introduction: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further., Patients and Methods: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed., Results: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred., Conclusion: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL., (Copyright © 2023 Copyright: © 2023 Journal of Minimal Access Surgery.)

Normal-functioning endothelium is crucial to maintaining vascular homeostasis and inhibiting the development and progression of cardiovascular diseases such as atherosclerosis. Exercise training has been proven effective in regulating arterial endothelial function, and the effect of this regulation is closely related to exercise intensity and the status of arterial endothelial function. With this review, we investigated the effects of the exercise of different intensity on the function of arterial endothelium and the underlying molecular biological mechanisms. Existing studies indicate that low-intensity exercise improves arterial endothelial function in individuals who manifest endothelial dysfunction relative to those with normal endothelial function. Most moderate-intensity exercise promotes endothelial function in individuals with both normal and impaired arterial endothelial function. Continuous high-intensity exercise can lead to impaired endothelial function, and high-intensity interval exercise can enhance both normal and impaired endothelial function. In addition, it was demonstrated that the production of vasomotor factors, oxidative stress, and inflammatory response is involved in the regulation of arterial endothelial function under different-intensity exercise interventions. We posit that this synthesis will then provide a theoretical basis for choosing the appropriate exercise intensity and optimize the prescription of clinical exercise for persons with normal and impaired endothelium., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: The relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclear., Objective: To prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China., Methods: A total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93-12.68, 12.69-14.32, 14.33-16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk., Results: We identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07-1.47), 56% (HR: 1.56, 95% CI: 1.31-1.86) and 91% (HR: 1.91, 95% CI: 1.59-2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD., Conclusion: Long-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Guan, Shi, Xu, Chen, Zhang, Dong, Gao, Wu and Xia.)

Objectives: To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM)., Methods: A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT., Results: After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT ( P =0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT ( P <0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate ( P =0.02) and DFS rate ( P =0.04)., Conclusions: Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.

Background: Endoscopic lumbar interbody fusion is a new technology that is mostly used for single-segment and unilateral lumbar spine surgery. The purpose of this study is to introduce percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) with unilateral laminotomy for bilateral decompression (ULBD) for lumbar spondylolisthesis and evaluate the efficacy by comparing it with open posterior lumbar interbody fusion (PLIF)., Methods: Twenty-eight patients were enrolled in PE-PLIF with the ULBD group and the open PLIF group. The perioperative data of the two groups were compared to evaluate the safety of PE-PLIF with ULBD. The visual analog scale (VAS) back pain, VAS leg pain, and Oswestry Disability Index (ODI) scores of the two groups preoperatively and postoperatively were compared to evaluate clinical efficacy. Preoperative and postoperative imaging data were collected to evaluate the effectiveness of the operation., Results: No differences in baseline data were found between the two groups ( p  > 0.05). The operation time in PE-PLIF with the ULBD group (221.2 ± 32.9 min) was significantly longer than that in the PLIF group (138.4 ± 25.7 min) ( p  < 0.05), and the estimated blood loss and postoperative hospitalization were lower than those of the PLIF group ( p  < 0.05). The postoperative VAS and ODI scores were significantly improved in both groups ( p  < 0.05), but the postoperative VAS back pain score in the PE-PLIF group was significantly lower than that in the PLIF group ( p  < 0.05). The excellent and good rates in both groups were 96.4% according to MacNab's criteria. The disc height and cross-sectional area of the spinal canal were significantly improved in the two groups after surgery ( p  < 0.05), with no difference between the groups ( p  > 0.05). The fusion rates in PE-PLIF with the ULBD group and the PLIF group were 89.3% and 92.9% ( p  > 0.05), respectively, the cage subsidence rates were 14.3% and 17.9% ( p  > 0.05), respectively, and the lumbar spondylolisthesis reduction rates were 92.72 ± 6.39% and 93.54 ± 5.21%, respectively ( p  > 0.05)., Conclusion: The results from this study indicate that ULBD can be successfully performed during PE-PLIF, and the combined procedure is a safe and reliable treatment method for lumbar spondylolisthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Li, Wu, Chang, Guan, Ma and Feng.)

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF)., Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure., Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD ( P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months., Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guan, Li, Zhao, Zhao, Yang, Dai, Dai, Gao, Xia and Dong.)

High glucose (HG) is one of the basic factors of diabetic nephropathy (DN), which leads to high morbidity and disability. During DN, the expression of glomerular glucose transporter 1 (GLUT1) increases, but the relationship between HG and GLUT1 is unclear. Glomerular mesangial cells (GMCs) have multiple roles in HG-induced DN. Here, we report prominent glomerular dysfunction, especially GMC abnormalities, in DN mice, which is closely related to GLUT1 alteration. In vivo studies have shown that BBR can alleviate pathological changes and abnormal renal function indicators of DN mice. In vitro, BBR (30, 60 and 90 μmol/L) not only increased the proportion of G1 phase cells but also reduced the proportion of S phase cells under HG conditions at different times. BBR (60 μmol/L) significantly reduced the expression of PI3K-p85, p-Akt, p-AS160, membrane-bound GLUT1 and cyclin D1, but had almost no effect on total protein. Furthermore, BBR significantly declined the glucose uptake and retarded cyclin D1-mediated GMC cell cycle arrest in the G1 phase. This study demonstrated that BBR can inhibit the development of DN, which may be due to BBR inhibiting the PI3K/Akt/AS160/GLUT1 signalling pathway to regulate HG-induced abnormal GMC proliferation and the cell cycle, supporting BBR as a potential therapeutic drug for DN., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objectives: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy., Methods: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate., Results: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children ( P <0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity ( P >0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML ( P <0.05)., Conclusions: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Objectives: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria., Methods: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group ( n =28) and myeloid expression group ( n =11). The clinical features, treatment, and prognosis were compared between the two groups., Results: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% ( P <0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P <0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1 , positive MLL-r , and hyperleukocytosis (white blood cell count ≥50×10 9 /L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P> 0.05)., Conclusions: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

Objective: The present study aimed to screen the differentially expressed (DE) circular RNAs (circ-RNAs) between lumbar intervertebral disc degeneration (IVDD) and normal tissues., Materials and Methods: In this experimental study, microarray hybridization was performed to evaluate circ-RNA expression, and the DE circ-RNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Host genes of DE circ-RNAs were predicted, and their functions were evaluated. Further, a competitive endogenesis (ce) RNA network among 4 DE circ-RNAs-miRNA-mRNA was constructed by Cytoscape., Results: A total of 2636 circ-RNAs were detected in all samples; among them, 89.23% were exonic circ-RNAs. There were 138 DE circ-RNAs, including 134 up-regulated circ-RNAs and 4 downregulated circ-RNAs in IVDD samples. qRT-PCR validation experiments showed that expression trends of hsa&#95;circ&#95;0003239, hsa&#95;circ&#95;0003162, hsa&#95;circ&#95;0005918, and hsa&#95;circ&#95;0005556 were in line with the microarray analysis results. Functional enrichment analysis showed that host genes of DE circ-RNAs significantly disturbed pathways of regulation of actin cytoskeleton, propanoate metabolism, and ErbB signaling pathway. The four DE circ-RNAs related ceRNA network was constructed., Conclusion: Our results revealed that circ-RNAs can function as miRNA sponges and regulate parent gene expression to affect IVDD., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Objective: To establish an efficient method for extracting exosomes from large-volume cell perfusate. Methods: EA.HY926, an immortalized cell line produced by the hybridization of human umbilical vein endothelial cells and human lung adenocarcinoma cell line A549, was cultured with M199 culture medium containing 10% fetal bovine serum. Flexcell STR-4000 parallel plate flow chamber system was employed to apply shear stress to EA.HY926. And then the perfusate was collected. The cell debris was removed by centrifugation. The supernatant was freeze-dried into the dry powder and was resuspended by small-volume medium. The dialysis was used to desalt and purify the suspension. The exoEasy Maxi Kit was used to extract the exosomes. The morphology of exosomes was observed by electron microscopy. The size of exosomes was detected by nanometer particle size analyzer. The activity of exosomes was detected by PKH26 staining. BCA protein quantification method was used to detect the protein concentration of exosomes. The expressions of exosomal specific proteins CD9 and CD81 were detected by Western blot. The quantitative RT-PCR was used to detect the expression of related genes in the exosomes. Results: The exosomes extracted by this method were uniform in size, showing a typical and complete vesicle-like structure. The particle size was concentrated at 30～150 nm, and the peak value was at 97.63 nm, indicating that the size was appropriate and the purity was high. Moreover, exosomes-specific protein CD9 and CD81 were expressed. PKH26 could bind to the membranous structure of exosomes and exosomes could be efficiently taken up by cells. Endothelial cells-associated CD31, vWF mRNA, and microRNA molecules such as miR-126, miR-21, miR-155 were expressed in exosomes secreted by EA.HY926. Conclusion: This method can effectively extract structurally intact, high-concentration, high-quality exosomes from large-volume cell perfusate.

Objective: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs., Methods: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs., Results: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028)., Conclusions: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

Objective: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation., Methods: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV)，human metapneumoviros(hMPV)，coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed., Results: Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%., Conclusion: Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.

Aims: This study aimed to investigate the characteristics and mechanism of autophagy on podocyte apoptosis under high glucose (HG) conditions and further explore the effect of berberine on podocyte autophagy, apoptosis and the potential mechanism., Materials and Methods: The levels of LC3II/I in podocytes stimulated with HG were detected at 0, 2, 4, 8, 12, 24, 36 and 48 h by western blotting. CCK-8 was used to detect the viability of podocytes. The level of autophagy was detected by western blotting, transmission electron microscopy and immunofluorescence. Podocyte apoptosis was analysed by using Hoechst staining, western blotting, annexin V/propidium iodide dual staining, and confocal microscopy. Then, podocytes were transfected with siRNA to silence mTOR, and the expression levels of proteins and mRNA involved in the mTOR/P70S6K/4EBP1 pathway were further investigated by western blotting and qRT-PCR., Key Findings: In this study, we found significantly reduced LC3II/LC3I and increased p62 in podocytes stimulated with HG for 24 h, and the level of autophagy reached a minimum at 24 h. Berberine restored podocyte viability and significantly attenuated HG-mediated inhibition of autophagy, as evidenced by the increased expression of LC3II/LC3I, the number of autophagosomes and the inhibition of p62. Moreover, berberine counteracted HG-induced podocyte apoptosis and injury, which was negatively correlated with the autophagy effect. Notably, silencing mTOR with siRNA augmented the inhibition of P70S6k and 4EBP1 phosphorylation, which was similar to the effect of berberine., Significance: Berberine activates podocyte autophagy by inhibiting the mTOR/P70S6K/4EBP1 signaling pathway, thereby alleviating podocyte apoptosis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Citri Reticulatae Pericarpium (CRP), the dried pericarp of Citrus reticulata Blanco, can be divided into "Guangchenpi" (GCP, the dried pericarps derived from Citrus reticulata 'Chachi') and "Chenpi" (CP, the dried pericarps derived from other cultivars of Citrus reticulata Blanco). To discriminate between GCP and CP, a simple and reliable high-performance thin-layer chromatography (HPTLC) method was firstly developed to analyze the volatile compound dimethyl anthranilate, and a high-performance liquid chromatography (HPLC) method was established to simultaneously quantify dimethyl anthranilate and three predominant flavonoids (hesperidin, nobiletin and tangeretin) in CRP samples. Both the HPTLC analysis and HPLC-orthogonal partial least squares discrimination analysis (OPLS-DA) indicated that GCP can be effectively distinguished from CP based on analysis of dimethyl anthranilate. Our results indicated that dimethyl anthranilate can be used as a marker compound for discrimination of GCP and CP. This work provided a convenient approach which might be applied for quality evaluation of CRP., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Many diseases have been associated with intestinal microbial dysbiosis. Host-microbial interactions regulate immune function, which influences the development of gastric cancer., Aims: The aims were to investigate the characteristics of intestinal microbiota composition in gastric cancer patients and correlations between the intestinal microbiota and cellular immunity., Methods: Fecal samples were collected from 116 gastric cancer patients and 88 healthy controls from Shanxi Province, China. The intestinal microbiota was investigated by 16S rRNA gene sequencing. Peripheral blood samples were also collected from the 66 gastric cancer patients and 46 healthy controls. The populations of peripheral T lymphocyte subpopulations and NK cells were analyzed by flow cytometry., Results: The intestinal microbiota in gastric cancer patients was characterized by increased species richness, decreased butyrate-producing bacteria, and the enrichment of other symbiotic bacteria, especially Lactobacillus, Escherichia, and Klebsiella. Lactobacillus and Lachnospira were key species in the network of gastric cancer-associated bacterial genera. The combination of the genera Lachnospira, Lactobacillus, Streptococcus, Veillonella, and Tyzzerella&#95;3 showed good performance in distinguishing gastric cancer patients from healthy controls. There was no significant difference in enterotype distribution between healthy controls and gastric cancer patients. The percentage of CD3 + T cells was positively correlated with the abundance of Lactobacillus and Streptococcus, and CD3 + T cells, CD4 + T cells, and NK cells were associated with Lachnospiraceae taxa., Conclusions: Our study revealed a dysbiotic intestinal microbiota in gastric cancer patients. The abundance of some intestinal bacterial genera was correlated with the population of peripheral immune cells.

Objective: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo., Methods: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR)., Results: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis., Conclusion: The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The present study aimed to evaluate the effects of Krüppel‑like factor 2 (KLF2) on the differentiation of endothelial progenitor cells (EPCs) to endothelial cells (ECs) induced by shear stress, and to investigate the corresponding mechanisms. Cultured rat late EPCs were exposed to shear stress (12 dyn/cm2) for different lengths of time. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to measure the initial KLF2 mRNA levels in each group. Subsequently, the EPCs were treated with anti‑integrin β1 or β3 antibodies to block integrin β1 and β3, respectively, or cytochalasin D to destroy F‑actin, and the subsequent expression levels of KLF2 in EPCs were measured. Then, KLF2 small interfering RNAs (siRNAs) were transfected into EPCs, and RT‑qPCR was used to measure the mRNA expression level of KLF2. Additionally, flow cytometry was applied to evaluate the protein levels of cluster of differentiation 31 (CD31) and the von Willebrand factor (vWF), and the regulatory effects of KLF2 in the promoter region of vWF were determined via a luciferase assay. High shear stress upregulated KLF2 expression, while blocking integrin β1/β3 or destroying F‑actin resulted in a corresponding decrease in KLF2 expression. Downregulation of KLF2 expression by siKLF2 inhibited the differentiation of EPCs to ECs under shear stress conditions, while the expression of EC‑specific markers decreased, including CD31 and vWF. Various lengths of the vWF promoter region induced vWF expression, and EPCs co‑transfected with KLF2 significantly increased the vWF expression levels compared with the group treated with vWF alone (P<0.01). In conclusion, shear stress may upregulate KLF2 expression, which may be associated with the integrin‑actin cytoskeleton system. Most importantly, the shear stress‑induced differentiation of EPCs may be mediated by KLF2.

Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells. Concurrently, aescin increased the expression of TIGAR, ROS levels, and autophagy activation. Knockdown of TIGAR enhanced the anticancer effects of aescin in vitro and in vivo, whereas overexpression of TIGAR or replenishing TIGAR downstream products, NADPH and ribose, attenuated aescin-induced apoptosis. Furthermore, aescin-induced ROS elevation and autophagy activation were further strengthened by TIGAR knockdown in HCT-116 cells. However, autophagy inhibition by knockdown of autophagy-related gene ATG5 or 3-methyladenine (3-MA) exaggerated aescin-induced apoptosis when TIGAR was knocked down. In conclusion, TIGAR plays a dual role in determining cancer cell fate via inhibiting both apoptosis and autophagy in response to aescin, which indicated that inhibition of TIGAR and/or autophagy may be a junctional therapeutic target in treatment of cancers with aescin.

Objective: High blood pressure (hypertension) is one of the most common cardiovascular diseases. In recent years, there were more and more studies on the function of inflammation in hypertension. CD68 mainly mediates the activation of cytokine interleukin-17 (IL-17) signaling pathway and participates in inflammatory responses. It has been studied the function of CD68 and IL-17 in hypertension, but it has not been reported whether it affected hypertension and vascular remodeling when macrophage CD68 expression inhibited. In this study, antisense-CD68 mice were used to study the effect and mechanism of angiotensin II-induced hypertensive vascular remodeling under specific suppression of macrophage CD68., Materials and Methods: Fifty 8-week-old male antisense-CD681 and C57 mice were divided into control and experimental group (angiotensin II group, 1000 ng•kg-1•min-1). After infusion of angiotensin II for 28 days, hematoxylin-eosin (HE) staining and immunohistochemical staining were used to observe the remodel of vascular. The changes of aortic inflammatory factors were detected by Real-time PCR (RT-PCR) and Western blotting., Results: By specifically inhibiting the expression of macrophage CD68, macrophage infiltration was mitigated in Ang II-induced hypertensive vascular remodeling model mouse, which also down-regulated the expression of vascular tissue inflammatory factor and activation of vascular smooth muscle cell p65., Conclusions: CD68 regulates the Ang II-induced hypertensive vascular remodeling through mediating macrophage inflammatory factor release.

Aims: Chemokine-mediated monocyte infiltration into the damaged heart represents an initial step in inflammation during cardiac remodelling. Our recent study demonstrates a central role for chemokine receptor CXCR2 in monocyte recruitment and hypertension; however, the role of chemokine CXCL1 and its receptor CXCR2 in angiotensin II (Ang II)-induced cardiac remodelling remain unknown., Methods and Results: Angiotensin II (1000 ng kg-1 min-1) was administrated to wild-type (WT) mice treated with CXCL1 neutralizing antibody or CXCR2 inhibitor SB265610, knockout (CXCR2 KO) or bone marrow (BM) reconstituted chimeric mice for 14 days. Microarray revealed that CXCL1 was the most highly upregulated chemokine in the WT heart at Day 1 after Ang II infusion. The CXCR2 expression and the CXCR2+ immune cells were time-dependently increased in Ang II-infused hearts. Moreover, administration of CXCL1 neutralizing antibody markedly prevented Ang II-induced hypertension, cardiac dysfunction, hypertrophy, fibrosis, and macrophage accumulation compared with Immunoglobulin G (IgG) control. Furthermore, Ang II-induced cardiac remodelling and inflammatory response were also significantly attenuated in CXCR2 KO mice and in WT mice treated with SB265610 or transplanted with CXCR2-deficienct BM cells. Co-culture experiments in vitro further confirmed that CXCR2 deficiency inhibited macrophage migration and activation, and attenuated Ang II-induced cardiomyocyte hypertrophy and fibroblast differentiation through multiple signalling pathways. Notably, circulating CXCL1 level and CXCR2+ monocytes were higher in patients with heart failure compared with normotensive individuals., Conclusions: Angiotensin II-induced infiltration of monocytes in the heart is largely mediated by CXCL1-CXCR2 signalling which initiates and aggravates cardiac remodelling. Inhibition of CXCL1 and/or CXCR2 may represent new therapeutic targets for treating hypertensive heart diseases.

Objective: To investigate the effects of endothelial progenitor cells (EPCs) under shear stress on the biological function such as proliferation, adhesion, migration, apoptosis and expression of α-smooth muscle actin (α-SMA), collagen-I and collagen-Ⅲ of hepatic stellate cells (HSCs)., Methods: HSCs and EPCs were inoculated into the upper and lower layers of the co-culture chamber respectively and co-incubated for 24 hours. Then, 12 dyne/cm 2 shear stress was applied to EPCs cells for another 24 hours. After that, proliferation, adhesion, migration and apoptosis of HSCs were detected by cell counting kit-8 (CCK-8) kit, cell adherent assay, Boyden cell migration assay and flow cytometry respectively. Fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression of alpha -SMA, collagen I and collagen-Ⅲ in HSCs., Results: Under shear stress, EPCs ecological niche could obviously inhibit the proliferation, adhesion and migration of HSCs, promote the apoptosis of HSCs, and down-regulate the mRNA and protein expression of collagen-I, collagen-Ⅲ in HSC cells., Conclusions: Under shear stress, EPCs ecological niche could inhibit the fibrosis development of HSCs to a certain extent.

This prospective study included 68,759 Chinese male adults from Kailuan cohort of China who had a standardized medical examination between 2006 and 2007 and were followed up for approximately 8 years until occurrence of ASCVD, cancer or death or until December 31, 2014. Subjects were divided into four categories based on the quartiles of TC, LDL-C and non-HDL-C. Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). During follow-up, 2,916 males developed ASCVD and 1,884 developed cancer. Compared with the lowest quartile, the upper-most quartiles of TC, LDL-C and non-HDL-C were all associated with increased ASCVD risk (HR 1.53; HR 1.16; HR 1.55); however, the upper-most quartiles of TC, LDL-C and non-HDL-C were all negatively associated with cancer (HR0.84; HR 0.82; HR 0.80) and these associations were present after exclusion of incident cancers during the first 4 years of follow-up. In a word, we report that high TC, LDL-C and non-HDL-C concentrations increased ASCVD incidence in a male population and that these lipid profiles were inversely associated with total cancer and several individual cancers., (© 2017 UICC.)

Objective: To investigate the characteristics and prognostic factor of central nervous system (CNS) involvement in patients with hemophagocytic lymphohistiocytosis (HLH) . Methods: From January 2006 to October 2015, 152 patients with HLH, 88 patients had CNS involvement, their clinical data were collected, and survival was analyzed using the Kaplan-Meier life table method, univariate and multivariate Cox regression model analyses were applied to identify the risk factors of prognosis. Results: ①57.9% patients complicated with neurological symptoms, cerebrospinal fluid abnormalities were observed in 37.0% patients, 57.5% patients had abnormal neuroradiology. ②36 patients survived well, 3 patients lost to follow-up, 49 dead, 1 survival patient had epilepsy. ③The 3-year overall survival rate of 88 patients was 44%. ④abnormal CSF and unreceived IT bore a significant, independent adverse prognostic value ( P <0.05) . Conclusion: CNS involvement in HLH has a high frequency and poor prognosis, few patients remained neurologic sequelae; abnormal CSF related to poor prognosis, positive intrathecal injections could improve the prognosis.

The purpose of this study was to profile altered patterns of gene expression that characterize abdominal aortic aneurysm and to compare these patterns between different conditions, unruptured (URA) and ruptured (RA). Full-thickness aortic wall tissues were obtained from patients during surgical repair of abdominal aortic aneurysm, including unruptured (n=29) and ruptured (n=11). RNA, protein and blood samples were prepared for each specimen, and differential levels of gene expression between unruptured and ruptured abdominal aortic tissues were assessed by immunohistochemistry, RT-qPCR and ELISA assays. Biochemical assay showed that triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL) concentration in the peripheral blood of URA and UA patients with large size of aneurysm (>5 cm) was significantly increased compared with those with small size of aneurysm (3-5 cm). Of 7 genes examined, TRPV1, CAM, TNF-α, IL-6, MCP-1 and VCAM were significantly increased in RA patients compared with URA patients, which also showed markedly increased expression in large size of aneurysm, with TRPV1 and CAM exception in RA patients. Only PPARδ expression observed decrease in RA patients with larger size of aneurysm. Taken together, URA and RA exhibit distinct patterns of gene expression, with most alterations being unique to this disease. Abdominal aortic aneurysm arising in different sizes of aneurysm is thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms., Competing Interests: None., (IJCEP Copyright © 2017.)

Objective: To study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance., Methods: Quantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively., Results: The mRNA levels of integrins β 2 , β 3 , and β 5 were significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin β 3 expression was associated with lower white blood cell counts (<100×10 9 /L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin β 5 expression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin β 3 expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05)., Conclusions: β-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin β5 is closely related to the risk of relapse of T-ALL. The expression of integrin β3 is closely related the treatment response and prognosis of T-ALL.

Objective: To investigate the correlation between the expression level of PRPS1 and the clinical characteristics in children with acute leukemia(AL)., Methods: Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 mRNA and protein expression in bone marrow samples from 176 patients diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete remission), and its relevance with clinical indicators was statistically analyzed. The bone marrow samples from 21 children with non-malignant hematological disease were used as controls., Results: (1)In B-ALL group, the level of PRPS1 mRNA in newly diagnosed patients were significantly higher than that in control and than that in complete remission patients (both P<0.0001). In T-ALL and AML group, differences was only observed between newly diagnosed patients and complete remission patients(both P<0.0001); (2)In B-ALL group, the expression level of PRPS1 increase with along risk enhancement (P<0.01), while no significant difference was observed in T-ALL (P>0.05). In AML patients, expression difference was shown between low risk group and high risk group(P<0.05); (3)High PRPS1 mRNA expression level were associated with high WBC counts and MRD positive in B-ALL patients (P=0.020, P=0.026, respectively); (4)Expression of NT5C2, an essential gene for relapse and drug resistance, was found to be positively correlated with PRPS1 expression in AL samples(P<0.05)., Conclusion: High expression of PRPS1 is relevant factor of unfavourable prognosis in B-ALL children, which suggest PRPS1 may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.

Adenomyosis, a benign invasion of endometrium, is closely related to endometriosis. Cysteine-rich 61 (Cyr61), a protein present in all endometrial tissues and menstrual effluents, is known to be associated with endometriosis. However, its relation to adenomyosis has not been determined thus far. Therefore, here, we aimed to investigate the expression of Cyr61 protein in adenomyosis and determine the correlation between Cyr61 expression and clinicopathologic parameters in patients with adenomyosis. One hundred and twenty patients with histologically diagnosed adenomyosis, who underwent hysterectomy for non-endometrial disease were enrolled in this study. Patients were interviewed using a standard questionnaire consisting of sociodemographic characteristics and reproduction history. The severity of dysmenorrhea and menorrhagia was evaluated using the visual analogue scale (VAS) and pictorial blood-loss assessment chart (PBAC). Samples of serum, endometrial tissue, and peritoneal fluid were collected, and Cyr61 mRNA levels were determined by RT-PCR. The Cyr61 protein levels in endometrial and ectopic lesions were determined by immunohistochemistry and those in serum and peritoneal fluid, by ELISA. We found that expression of Cyr61 was higher in the ectopic endometrium than in the eutopic endometrium. Cyr61 expression in the endometrium was correlated with age, number of natural labors, PBAC score, VAS score, uterine volume, adenomyosis type, and concurrent endometriosis. The Cyr61 protein level in the ascites was higher than that in serum, and no correlation existed between them. Our results suggest that the expression of Cyr61 may be indirectly related to the degree of dysmenorrhea and Cyr61 may be involved in the pathogenesis of adenomyosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Carboxyl terminus of Hsp70-interacting protein (CHIP) is a critical ubiquitin ligase/cochaperone to reduce cardiac oxidative stress, inflammation, cardiomyocyte apoptosis and autophage etc. However, it is unclear whether overexpression of CHIP in the heart would exert protective effects against DOX-induced cardiomyopathy. Cardiac-specific CHIP transgenic (CHIP-TG) mice and the wild-type (WT) littermates were treated with DOX or saline. DOX-induced cardiac atrophy, dysfunction, inflammation, oxidative stress and cardiomyocyte apoptosis were significantly attenuated in CHIP-TG mice. CHIP-TG mice also showed higher survival rate than that of WT mice (40% versus 10%) after 10-day administration of DOX. In contrast, knockdown of CHIP by siRNA in vitro further enhanced DOX-induced cardiotoxic effects. Global gene microarray assay revealed that after DOX-treatment, differentially expressed genes between WT and CHIP-TG mice were mainly involved in apoptosis, atrophy, immune/inflammation and oxidative stress. Mechanistically, CHIP directly promotes ubiquitin-mediated degradation of p53 and SHP-1, which results in activation of ERK1/2 and STAT3 pathways thereby ameliorating DOX-induced cardiac toxicity.

Background: Single port laparoscopic surgery (SPLS) is an innovative approach that is rapidly gaining recognition worldwide. The aim of this study was to determine the feasibility and safety of SPLS compared to conventional laparoscopic surgery for the treatment of benign adnexal masses., Methods: In total, 99 patients who underwent SPLS for benign adnexal masses between December 2013 and March 2015 were compared to a nonrandomized control group comprising 104 conventional laparoscopic adnexal surgeries that were performed during the same period. We retrospectively analyzed multiple clinical characteristics and operative outcomes of all the patients, including age, body mass index, size and pathological type of ovarian mass, operative time, estimated blood loss (EBL), duration of postoperative hospital stay, etc., Results: No significant difference was observed between the two groups regarding preoperative baseline characteristics. However, the pathological results between the two groups were found to be slightly different. The most common pathological type in the SPLS group was mature cystic teratoma, whereas endometrioma was more commonly seen in the control group. Otherwise, the two groups had comparable surgical outcomes, including the median operation time (51 min vs. 52 min, P = 0.909), the median decreased level of hemoglobin from preoperation to postoperation day 3 (10 g/L vs. 10 g/L, P = 0.795), and the median duration of postoperative hospital stay (3 days vs. 3 days, P = 0.168). In SPLS groups, the median EBL and the anal exsufflation time were significantly less than those of the conventional group (5 ml vs. 10 ml, P < 0.001; 10 h vs. 22 h, P < 0.001)., Conclusions: SPLS is a feasible and safe approach for the treatment of benign adnexal masses. Further study is required to better determine whether SPLS has significant benefits compared to conventional techniques.

Objective: To analyze and summarize the clinical characteristics, laboratory tests and treatment of X-linked lymphoproliferative syndrome type 1 (XLP-1)., Method: A retrospective study was done in 2012 on an XLP-1 patient to collect the data on clinical manifestation, laboratory examination, gene and protein expression, complications and prognosis. Literatures were reviewed in Pubmed with the key word"X-linked lymphoproliferative syndrome"., Result: The patient with persistent high fever, jaundice, abdominal distension, hepatosplenomegaly and lymphadenectasis, rash and suspicious positive family history; the patient eventually died of hemophagocytic lymphohistiocytosis (HLH), with intestinal perforation, intestinal infection and bleeding after being infected with EB virus. This patient with SH2D1A gene exon 1 large fragment of the coding region of the nucleotide deletion and insertion mutations causing missense mutations (p.Leu25Lys) and nonsense mutations (stop codon TAG was inserted after missense mutation so that the protein encoded by the early termination of the 25 amino acids), which led to SAP protein missing. The expression of SAP in his mother was also partly missing. Retrieval of reports on XLP-1 was conducted through literature search (included totally 157 cases) at home and abroad, positive family history accounted for 60.6%(40/66); lymphoma incidence accounted for 49.7%(72/145); low gamma globulin occurred in 24.8%(39/157) of cases; secondary HLH ratio accounted for 43.3%(68/157); XLP-1 in patients with hemorrhagic enteritis and gastritis was low, accounted for only 2.6%(3/116)., Conclusion: XLP-1 patients occasionally develop necrotic enteritis complicated with ileal perforation.XLP-1 with large fragment deletion of SH2D1A gene might be associated with serious gastrointestinal manifestations.

Objective: To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL)., Methods: The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed., Results: Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5%). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months., Conclusion: Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.

Objective: To observe the effect of miR-467b on the atherosclerosis (AS) of rats with apolipoprotein E (ApoE) gene knockout (ApoE(-/-))., Methods: ApoE(-/-) rats were fed with high fat and high cholesterol diet and were randomly divided into group A, group B and group C, with 10 rats in each group. Group A: rats were injected with ApoE agonist through the caudal vein; group B: rats were injected with ApoE antagonist through the caudal vein; group C: as negative control group. Enzyme oxidation method was used to detect the blood lipid levels of rats. Western blotting method was used to detect the aortic lipoprotein lipase (LPL) expression levels of rats. HE staining and oil red O staining were performed to observe the AS lesions and lipid accumulation state., Results: Compared with group C, blood lipid level, aortic intima and aortic sinus lipid accumulation area ratio, aortic sinus lesion area and LPL expression level in group A significantly reduced; while blood lipid level, aortic intima and aortic sinus lipid accumulation area ratio, aortic sinus lesion area, and LPL expression level in group B significantly increased, with the statistical difference (P < 0.05)., Conclusions: miR-467b can alleviate the AS lesions of ApoE(-/-) rats, and its inhibiting effect on AS may be related to LPL expression., (Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: Mixed endometrial stromal and smooth muscle tumor (MESSMT)-a rare mesenchymal uterine tumor of the uterus with atypical clinical symptoms-is susceptible to misdiagnosis and missed diagnosis. We report a case of a disseminated MESSMT with intravenous and intracardiac extensions treated with staging surgery and review previously documented cases of such tumors with intracardiac extension., Case Report: The case involves a 45-year-old woman with disseminated MESSMT that originated in the uterus and progressed through the iliac vein, inferior vena cava, right atrium, and into the right ventricle, which closely resembled intravenous leiomyomatosis (IVL) grossly and microscopically. She presented with a 1-year history of dyspnea on exertion. IVL was highly suspected preoperatively based on computed tomography and magnetic resonance imaging findings. Two-stage surgeries were performed successfully. The postoperative pathology indicated a disseminated MESSMT., Conclusion: This case illustrates the important role of pathology and immunohistochemistry in the differential diagnosis of a rare tumor that mimics the characteristics of IVL with intracardiac involvement and demonstrates the therapeutic strategy for this rare entity., (Copyright © 2015. Published by Elsevier B.V.)

Background: Skin appearance is influenced by biophysical parameters. Seasonal changes affect the condition of normal skin and may trigger cutaneous disorders., Objectives: This study was undertaken to measure the effects of seasonal changes on biophysical parameters in the skin of female subjects living in Guangzhou City in southern China., Methods: A cross-sectional study was conducted in 178 healthy, adult Chinese women in whom forehead skin was examined in all four seasons between March 2007 and February 2008. Commercially available, non-invasive devices were used to measure skin hydration, sebum content, pH, and transepidermal water loss (TEWL) in a closed environment under controlled and constant conditions of temperature and humidity. Correlations between skin parameters and climate conditions were investigated., Results: There were significant seasonal changes in TEWL and pH (autumn and winter > spring and summer), skin hydration (spring and summer > autumn and winter), and sebum content (spring and summer > autumn and winter). Skin hydration was correlated with average temperature and humidity. Skin TEWL and skin pH were correlated with average temperature, humidity, and ultraviolet (UV) radiation levels. Skin sebum content was correlated with average humidity., Conclusions: Facial skin physiology showed seasonal variations in China. The reasons for the changes may refer to seasonal changes in temperature, humidity, and UV radiation., (© 2014 The International Society of Dermatology.)

Ex vivo expansion of endothelial progenitor cells (EPCs) may be a promising strategy to overcome the clinical problem of limited cell numbers. As the culture medium is the key for the cell characteristics, the effects of different culture media on EPCs were investigated in the present study. Rat bone marrow mononuclear cells were cultured in different media, including M-199 media with 20% fetal bovine serum (FBS) and bovine pituitary extract (M1); M-199 media with 10% FBS, 20 ng/ml vascular endothelial growth factor (VEGF) and 10 ng/ml basic fibroblast growth factor (bFGF; M2) or epidermal growth medium (EGM)-2MV media. The cell morphology and biological functions, such as proliferation, adhesion, migration, tube formation and nitric oxide (NO) production were subsequently assayed in vitro. Moreover, endothelial biomarkers and apoptosis were also analyzed. The results showed that endothelial‑like cells appeared in all of the culture systems. First‑passage cells, namely early EPCs, tended to form colonies in M2 and EGM-2MV media but showed a fusiform shape in M1 media. The 3rd or 4th generation EPCs, namely late EPCs, cultured in EGM-2MV media exhibited increased adhesion, migration, tube formation and NO production as compared with EPCs in M1 or M2 media. Furthermore, late EPCs cultured in EGM-2MV expressed higher levels of endothelial cell markers, such as von Willibrand factor (vWF)and CD31, but relatively greater levels of apoptosis were observed. In conclusion, cell culture conditions, for example the medium used, affects the biological properties of bone marrow-derived early and late EPCs.

Objective: The Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL., Methods: A total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0., Results: Toxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality., Conclusions: The drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

We developed a novel chitosan-based luminescent/magnetic hybrid nanoparticles with folate-conjugated tetrapeptide composites (CLMNPs-tetrapeptide-FA) by conjugation in situ. First, chitosan, CdTe quantum dots (QDs), and superparamagnetic iron oxide were directly gelled into ternary hybrid nanogels. Subsequently, tetrapeptides (GFFG and LGPV) and folate were conjugated orderly into the hybrid nanoparticles. The morphology, composition, and properties of the as-prepared copolymers have also been characterized and determined using TEM, EDX, XRD, FTIR spectra, DLS, fluorescence spectroscopy, VSM, and fluorescence microscopy imaging studies. The size range of the end product CLMNPs-tetrapeptide-FA copolymers was from 150 to 190 nm under simulated physiological environment. In vivo, the experimental results of magnetic accumulation showed that the copolymers could be trapped in the tumor tissue under magnetic guidance. Under the present experimental conditions, the loading efficiencies of CPT were approximately 8.6 wt % for CLMNPs-GFFG-FA and 1.1 wt % for CLMNPs-LGPV-FA, respectively. The CPT cumulative release under dialysis condition mainly occurred for the first 28 h, and could reach 55% at pH 5.3 and 46% at pH 7.4 from CPT-loaded CLMNPs-GFFG-FA, and 69% at pH 5.3 and 57% at pH 7.4 from CPT-loaded CLMNPs-LGPV-FA within 28 h, respectively. The hemolysis percentages (<2%) and coagulation properties of blank and CPT-loaded copolymers were within the scope of safe values. Compared to free CPT, the CPT-loaded CLMNPs-tetrapeptide-FA copolymers showed specific targeting to A549 cells in vitro. More than 75% viability in L02 cells were seen in CLMNPs-GFFG-FA and CLMNPs-LGPV-FA copolymer concentration of 500 μg/mL, respectively. It was found that the two kinds of copolymers were transported into the A549 cells by a folate-receptor-mediated endocytosis mechanism. These results indicate that the multifunctional CLMNPs-tetrapeptide-FA copolymers possess a moderate CPT loading efficiency, low cytotoxicity, and favorable biocompatibility, and are promising candidates for tumor-targeted drug delivery.

Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, and BRS-3 agonism is being explored as a possible therapy for obesity. Here we study the role of BRS-3 in the regulation of glucose-stimulated insulin secretion (GSIS) and glucose homeostasis. We quantified BRS-3 mRNA in pancreatic islets from multiple species and examined the acute effects of Bag-1, a selective BRS-3 agonist, on GSIS in mouse, rat, and human islets, and on oral glucose tolerance in mice. BRS-3 is highly expressed in human, mouse, rhesus, and dog (but not rat) pancreatic islets and in rodent insulinoma cell lines (INS-1 832/3 and MIN6). Silencing BRS-3 with small interfering RNA or pharmacological blockade with a BRS-3 antagonist, Bantag-1, reduced GSIS in 832/3 cells. In contrast, the BRS-3 agonist (Bag-1) increased GSIS in 832/3 and MIN6 cells. The augmentation of GSIS by Bag-1 was completely blocked by U73122, a phospholipase C inhibitor. Bag-1 also enhanced GSIS in islets isolated from wild-type, but not Brs3 knockout mice. In vivo, Bag-1 reduced glucose levels during oral glucose tolerance test in a BRS-3-dependent manner. BRS-3 agonists also increased GSIS in human islets. These results identify a potential role for BRS-3 in islet physiology, with agonism directly promoting GSIS. Thus, in addition to its potential role in the treatment of obesity, BRS-3 may also regulate blood glucose levels and have a role in the treatment of diabetes mellitus.

We report herein the discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 (BRS-3) agonists and their unusual chirality. Starting from a high-throughput screening lead, we prepared a series of BRS-3 agonists with improved potency and pharmacokinetic properties, of which compound 8a caused mechanism-based, dose-dependent food intake reduction and body weight loss after oral dosing in diet-induced obese mice. This effort also led to the discovery of a novel family of chiral molecules originated from the conformationally constrained seven-membered diazepine ring.