Objective:To analyze the dynamic changes of neutrophil percentage-to-albumin ratio (NPAR) during treatment with bortezomib-lenalidomide-dexamethasone (VRD) in patients with multiple myeloma (MM),and explore the relationship between NPAR value and short-term prognosis of MM patients. Method:The data of 80 MM patients who underwent VRD chemotherapy at Tangshan Workers Hospital from January 2019 to April 2021 were retrospectively analyzed. NPAR levels were measured before VRD chemotherapy (T0),and on the first day of the third (T1),sixth (T2),and eighth (T3) chemotherapy cycles. All patients were followed up for 1 year,with the recurrence,progression,or death occurring within 1 year after the completion of VRD treatment as the endpoint event. The patients were divided into a good prognosis group and a poor prognosis group based on the follow-up results. The changes in NPAR at T0,T1,T2,and T3 in the two groups were statistically analyzed. The restricted cubic spline method was used to analyzed the relationship between NPAR and adverse short-term prognosis in MM patients undergoing VRD chemotherapy. Results:Among the 80 MM patients,25 cases (31.25％) had poor short-term prognosis,including 19 cases (23.75％) of progression or recurrence,and 6 cases (7.50％) of all-cause mortality. The levels of neutrophils and NPAR in the poor prognosis group at T0,T1,T2 and T3 were higher than those in the good prognosis group at the same period,while the albumin levels in the poor prognosis group at T0,T1,and T2 were lower than those in the good prognosis group at the same period (P<0.05);There was no significant difference in albumin levels between the poor prognosis group and the good prognosis group at T3 (P>0.05). Within the poor prognosis group and the good prognosis group,the levels of neutrophils and NPAR decreased sequentially at T0,T1,T2,and T3,while the levels of albumin increased sequentially,and the differences between each stage were statistically significant (P<0.05). The restricted cubic spline model showed an approximate J-shaped curve between the risk of poor short-term prognosis and the pre-treatment NPAR level in MM patients (P<0.05). If the pre-treatment NPAR>0.52,the risk of poor short-term prognosis in MM patients increased with the increase of NPAR value. Conclusion:After VRD treatment,the NPAR value of MM patients gradually decreases,and there is a correlation between the NPAR value before VRD treatment and the risk of poor prognosis after treatment. If NPAR>0.52 before treatment,the higher the NPAR value,the higher the risk of poor short-term prognosis in MM patients.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.

OBJECTIVE: To study the association between maternal reduced folate carrier ( METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal CONCLUSIONS Maternal
Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Reduced Folate Carrier Protein/genetics* ; Risk Factors

Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg^-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.

Objective To investigate the clinical therapeutic methods and their curative effects in recurrent ischemic angina for internal mammary artery resterosis after coronary artery bypass grafting (CABG).Methods We enrolled the patients who had recurrence of ischemic angina for restenosis of internal mammary artery graft after CABG as research subjects in the Affiliated Hospital of Yan'an University from January 2014 to January 2016.The 42 patients were divided into three groups according to the different treatment approaches for recurrence of ischemic angina:Group A (n=22)who received internal mammary artery interventional therapy;Group B (n=12)who received coronary artery bypass grafting treatment;and Group C (n=8)who received left subclavian artery proximal stent treatment.Then we compared the clinical therapeutic effects in the three groups.Results The success rate in Group C was 100%,which was the highest in the three groups,and the post-operative restenosis rate was 0.The hospitalization time was significantly shorter in Group A than in Group B (P＜0.05).However,the two groups did not significantly differ in mortality,success rate or restenosis rate (P＞0.05).Conclusion We should select the appropriate treatment according to the patient's specific situation for recurrent ischemic angina. Endovascular treatment has evident therapeutic effects,rapid postoperative recovery,and lower treatment risk, making it the preferred treatment when possible.

BACKGROUND: All-trans retinoic acid (ATRA) is an ideal therapy for acute promyelocytic leukemia, which can induce promyelocytes to differentiate to mature granulocytes. However, differentiation syndrome is still a high risk for the patients undergoing ATRA therapy. Occurrence of this complication is closely related with cellular morphology change and expression and function of cellular adhesion molecules, especially selectin and integrin families. OBJECTIVE: To reveal rolling adhesion behavior and mechanical mechanism of ATRA treated HL-60 cells on the substrate coated with E-selectin under different fluid shear forces. METHODS: Using the equipment of parallel plate flow chamber, untreated and ATRA treated HL-60 cells were driven to roll on E-selectin-coated substrate. The mean rolling velocity and mean stop time were calculated. Here, the HL-60 cells were incubated in the medium containing 1×10-6mol/L ATRA for 0, 48, 72, 96 hours. The substrates were captured with 40 μg/L E-selectin overnight and the shear stresses were set to 0.02, 0.04, 0.06 Pa. RESULTS AND CONCLUSION: The velocity of untreated/treated HL-60 cells decreased firstly and then increased with monotonously increasing shear stress. On the contrary, the mean stop time and factional stop time increased firstly and then decreased. Therefore, we deduced that the flow enhanced rolling adhesion was regulated by the catch bond for the HL-60 cells rolling on E-selectin under flow. On the other side, rolling velocities decreased under the same shear stress even if treated with or without ATRA, and the mean stop time and factional stop time increased inversely, which further illustrate the rolling velocity is mainly regulated by stop time.

BACKGROUNDSeverity scoring systems are useful tools for measuring the severity of the disease and its outcome. This pilot study was to verify and compare the prognostic performance of the Simplified Acute Physiology Score II (SAPS II) and Glasgow Coma Scale (GCS) in neuro-intensive care unit (N-ICU) patients.

METHODSA total of 1684 patients consecutively admitted to the N-ICU at Xuanwu Hospital between January 1, 2005 and December 31, 2011 were enrolled in this study. The data-base included admission data, at 24-, 48-, and 72-hour SAPS II and GCS. Repeated measure data analysis of variance, Logistic regression analysis, the Hosmer-Lemeshow goodness-of-fit statistic, and the area under the receiver operating characteristic were used to evaluate the performance.

RESULTSThere was a significant difference between the SAPS II or GCS score at four time points (F = 16.110, P = 0.000 or F = 8.108, P = 0.000). The SAPS II scores or GCS score at four time points interacted with the outcomes with significant difference (F = 116.771, P = 0.000 or F = 65.316, P = 0.000). Calibration of the SAPS II or GCS score at each time point on all patients was good. The percentage of a risk estimate prediction corresponding to observed mortality was also good. The 72-hour score have the greatest consistency. Discriminations of the SAPS II or GCS score at each time were all satisfactory. The 72-hour score had the greatest discriminative power. The cut-off value was 33 (sensitivity of 85.2% and specificity of 74.3%) and 6 (sensitivity of 70.6% and specificity of 65.0%). The SAPS II at each time point on all patients showed better calibration, consistency and discrimination than GCS. The binary Logistic regression analysis identified physiological variables, GCS, age, and disease category as significant independent risk factors of death. After the two variables including underlying disease and type of admission were excluded, we built the simplified SAPS II model. A correlation was suggested between the simplified SAPS II score at each time point and outcome, regardless of the diagnosis.

CONCLUSIONSThe GCS scoring system tends to be a little weaker in the predictive power than the SAPS II scoring system in this Chinese cohort of N-ICU patients. The advantage of SAPS II scoring system still exists that it dose not need to take into account the diagnosis or diseases categories, even in the special N-ICU. The simplified SAPS II scoring system is considered a new idea for the estimation of effectiveness.

APACHE ; Adult ; Aged ; Aged, 80 and over ; China ; Female ; Glasgow Coma Scale ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Young Adult

UPLC-MS-MS system was used for the identification of arbidol metabolites in the rat feces, urine and plasma samples. The system was so powerful a way with high ability of separation and analysis, based on both chromatography and mass properties. The isotope of Br was also a good indicator for metabolites finding. There were altogether 9 metabolites detected and identified, including 2 phase I biotransformation products and 7 phase II ones. It is concluded that arbidol mainly undergo metabolic reactions such as N-demethylation, S-oxidation, glucuronidation and sulfation in rats.