Effect of advanced age on plasma homocysteine levels and its association with ischemic stroke in non-valvular atrial fibrillation

Background Elevated homocysteine （Hcy） has been reported to be associated with cardiovascular events in atrial fibrillation （AF） pa- tients, while the age-related expression pattern of plasma Hcy in AF remains unknown. The study was aimed to investigate the effect of ad- vanced age on plasma Hcy levels and its association with ischemic stroke in non-valvular AF patients. Methods A total of 2562 consecu- tive patients with non-valvular AF and 535 controls were enrolled and divided into six age groups. Plasma Hcy levels were analyzed among different age groups, and the effect of advanced age on Hcy was investigated. Results Plasma Hcy levels did not show any difference among groups aged below 65 years, while it increased sharply in patients aged 65-74 years and aged over 75 years （15.7 ±4.6 μmol/L, 17.1 ±4.9 μmol/L, both P 〈 0.01 compared with the first four age groups）. Hcy was much higher in AF patients than in controls at the same age group （all P 〈 0.05）. The proportion of patients with hyperhomocysteinemia increased gradually with age from 32.3%, 29.2%, 31.2%, 32.4%, 45.9%, to 51.4% in six age groups. The concentration of Hcy in AF patients with ischemic stroke increased progressively with age, and was higher than those without stroke at the same age. Logistic regression analysis demonstrated that age 65-74 years [odds ratios （OR）： 1.742, 95% confidence interval （CI）： 1.223-2.482, P = 0.002] and age ≥ 75 years （OR： 2.637, 95% CI： 1.605-4.335, P 〈 0.001） were significantly independent predictors of elevated plasma Hcy levels. Conclusions Advanced age was significantly associated with elevated Hcy levels, which may provide a possible explanation for the progressive increase in ischemic stroke especially in elderly AF patients.

Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

Background Endomyocardial biopsy （EMB） is an important tool when patients with inflammatoric cardiomyopathy （DCMi） are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB （Group 1 〉 70 years, n = 85; Group 3 〈 70 years; n = 418） were compared to patients of the same age group without evi- dence of DCMi on EMB （Group 2 〉 70 years, n = 45; Group 4 〈 70 years; n = 147）. Results Among 24,275 patients treated at our institu- tion during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 （2.1%） patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ~ 2.8 years, mean ejection fraction was 38% q- 14%. On presentation, signs of hemody- namic compromise （NYHA functional class IIUIV, low cardiac output/index, and low cardiac power index） were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B 19 （PVB） was frequently encountered in both age groups （Group 1： 69.4% vs. Group 2： 59.6%）; detection of more than one viral genome was more frequent in Group 1 （21.2% vs. 11.2%; P = 0.02） whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients 〉 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed.

Retrospective Cohort Study to Investigate Pregnancy Outcomes in a Population of Advanced Maternal Age Congolese Women of Kinshasa: A Study Protocol

Introduction: Pregnancies at advanced maternal age (AMA) are those occurring after the age of 35 years old. They carry a high risk of maternal-fetal morbidity and mortality, thus constituting a public health problem. Several African countries have reported an upward trend in both the age of childbirth and the frequency of women with AMA over the past 20 years. In the Democratic Republic of Congo (DRC), where maternal and neonatal morbidity and mortality remain very high, data on AMA pregnancies go back more than 20 years. Objective: We propose evaluating obstetrical outcomes among women in AMA in our setting and the associated factors. Methods: This retrospective cohort study will be conducted in two healthcare facilities (ESS) in Kinshasa. The study population will consist of all women who delivered a single fetus after 28 weeks of gestation between January 2012 and December 2022 (10 years) in the selected ESS. The data collected will be analyzed using R software version 4.2.0. Quantitative variables will be summarized as means with standard deviation or medians with interquartile range. Qualitative variables will be presented as proportions (%). Multivariate logistic regression will be used to determine the main maternal-fetal complications associated with AMA and predictors of obstetric outcomes. P Discussion: The high maternal and infant mortality rates in DRC are among the highest in the world. The context of maternal age has become a topic of growing interest due to its potential implications for the health of women and newborns, it is crucial to identify the risk factors associated with obstetric outcomes by identifying obstetrical outcomes associated with advanced maternal age in the DRC. Many Congolese women tend to start their maternity journey at a relatively young age. However, there is also an emerging trend towards delayed childbearing, particularly in urban areas and among women with access to education and family planning services. Conclusion: The results of this study will enable us to update the frequency of AMA pregnancies in our environment. The socio-demographic and clinical profile of these pregnancies will be determined. The main maternal-fetal complications associated with AMA in our setting and the associated factors will be identified.

Obstetric Outcomes in Advanced Maternal Age among Women at King Abdulaziz University Hospital

Background: Advanced maternal age, over 35 years, is a well-known risk factor for poor pregnancy outcomes. It is commonly associated with various pregnancy complications, such as spontaneous miscarriage, preeclampsia/ toxemia, gestational diabetes mellitus, preterm labor, stillbirth, chromosomal abnormalities, and cesarean delivery. Objectives: This study assessed obstetric and neonatal complications associated with advanced maternal age. Methods: We reviewed the medical records of 199 pregnant women over 35 years old at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, from January to June 2022. We gathered data on age, nationality, number of antenatal visits, results of ultrasound scans for dating and viability, nuchal translucency and anatomy surveys, medications and multivitamins taken during pregnancy, smoking status, pregnancy, and fetal complications, and mode of delivery. Results: The prevalence of obstetric complications was 71.4% (preeclampsia/toxemia, 4.5%;antepartum hemorrhage, 4%;postpartum hemorrhage, 1%;and gestational diabetes, 23.1%). The most frequent complication was preterm labor between 34 and 36 weeks (48%), and only 12.6% of all deliveries were associated with fetal and neonatal complications such as congenital anomalies and neonatal jaundice. The prevalence of anemia during pregnancy was 10.1%, 21.1%, and 28.6% in the first, second, and third trimesters, respectively, and pregnancies complicated with antepartum or postpartum hemorrhage were associated with higher rates of anemia in the second trimester. A significant relationship was found between mean maternal age (38.84 ± 2.75 years) and the development of maternal complications (p < 0.05). Newborns with neonatal complications were much more likely to be born to mothers with a history of antepartum hemorrhage and anemia in the second trimester. Conclusion: Our findings confirm that pregnancy at an advanced maternal age is associated with increased overall maternal complications. The most frequent complication was preterm labor (48%). Other complications, such as preeclampsia/toxemia, antepartum hemorrhage, postpartum hemorrhage, gestational diabetes, and anemia, were less frequent in the sample we reviewed.

Current treatment status in patients with severe aortic valve stenosis and outcome of long term follow-up at advanced age： a Chinese single center study

Background Surgical aortic valve replacement is the standard treatment for patients with severe aortic stenosis, but some registries have indicated that 30% to 60% of these patients are not treated surgically, usually due to advanced age and/or comorbidities. This single center study in China investigated the current treatment status in the patients with severe aortic stenosis and evaluated the long term clinical outcome in advanced age patients whether or not undergoing aortic valve replacement. Methods Clinical data of 867 consecutive patients with severe aortic stenosis between January 2000 and December 2006 were retrospectively analyzed. The patients 〉65 years old were followed up by telephone or information from medical records. The primary end-point was all-cause mortality. Results The patients＇ average age was （52±19） years （range, 1-91 years）, and 34% were women. The percentages of the patients aged 〈15 years, between 15 and 34 years, between 35 and 54 years, between 55 and 64 years, between 65 and 74 years, and 〉75 years who underwent surgical aortic valve replacement were 82.3%, 87.2%, 88.8%, 78.2%, 65.3% and 22.2% respectively. In the patients （n=256） 〉65 years old, 43.4% had New York Heart Association class III and IV symptoms, 39.1% had hypertension, 33.2% had coronary heart disease, and 3.1% had stroke. In the patients not undergoing aortic valve replacement, 1.6% had renal insufficiency, 4.7% had chronic obstructive pulmonary disease, 2.0% had critical hematopathy, and 0.4% had mammary cancer. A total of 186 （72.7%） patients finished the follow-up, and the average duration of the follow-up was （60±2.6） months. In the patients between 65 and 74 years old, the total deaths and cardiac deaths in the patients undergoing aortic valve replacement decreased significantly compared with those with conservative treatment （10.3% vs. 53.7%, P 〈0.001 and 6.3% vs. 50.7%, P〈0.001）. Similarly, in the patients ≥75 years old, there was a significant difference between patients who had surgery and those who had conservative treatment in the total deaths and cardiac deaths （21.4% vs. 63.3%, P=0.007 and 14.3% vs. 46.9%, P=0.033）. The total deaths in the patients aged between 65 and 74 years were significantly fewer compared with 〉75 years old patients （25.4% vs. 54.0%, P 〈0.001）. Cox regression revealed that aortic valve replacement was the only independent predictor of mortality （HR 0.183; 95% CI, 0.101-0.332, P 〈0.001 ）. Conclusions This single centre study showed that surgical aortic valve replacement was still the standard treatment for the patients with severe aortic stenosis and had a satisfying prognosis. However, the high risk patients with advanced age and comorbidities usually selected conservative treatment and had an unfavorable prognosis.

Guideline for Diagnosis and Treatment of Infertility in Advanced Age Women(Revised Edition)

As more and more couples postpone their childbearing plan,and Chinese two-child policy is fully liberalized,the proportion of advanced-age parents gradually increases.However,ovarian function gradually descends with age,and the incidences of uterine fibroids,scarred uterus,and pelvic inflammation disease significantly increase,which increases the risk of infertility.Even though the advanced-age women successfully get pregnant through assisted reproductive technology(ART),the risks of pregnancy complications and medical and surgical complications(such as miscarriage,gestational diabetes,gestational hypertension,intrauterine fetal death,low birth weight of newborn,or premature birth)will increase with age.Currently,the consistency of diagnosis and treatment strategies on elderly patients with infertility is still lacking,and the efficacy of the diagnosis and treatment is even worse.In light of the above situations,the specialized committee organized experts of reproductive endocrinology and ART to compose this guideline,aiming for standardizing the process of diagnosis and treatment on advanced-age infertile women.This guideline interprets reproductive status and related fertility evaluation on advanced-age infertile women,and discusses prepregnancy preparation of body and nutrition and consultation,as well as related risk assessment of pregnancy.It also analyzes the current clinical and laboratory hot issues:the genetic characteristics of advanced-age women,evaluation,counseling,and corresponding laboratory screening,diagnostic methods,and operational norms.In addition,for the advanced-age women with high incidence of medical and surgical complications,this guideline gives us norms of diagnosis and treatment on different complications.Finally,strategies of ART are made for the advanced-age infertile women,which can provide basis and guidance for their diagnosis and treatment.

Assisted Hatching in Couples with Advanced Maternal Age： A Systematic Review and Meta-analysis

This systematic review aimed to evaluate the efficacy and safety of assisted hatching （AH） performed in couples with advanced maternal age. We searched for randomized controlled trials （RCTs） in electronic databases, including MEDLINE, EMBASE and CENTRAL （from inception to January 2018）; in addition, we hand-searched the reference lists of included studies and similar reviews. We included RCTs comparing AH versus no treatment （control）. The meta-analysis was performed by RevMan 5.3 software. The search retrieved 943 records and 8 RCTs were included, comprising 870 cycles （n=440 for AH, and n=430 for control）. There was no significant difference in the rates of live birth （RR 0.88, 95% CI 0.65 to 1.18, 3 RCTs, n-427,I^2=0%）, clinical pregnancy （RR 1.00, 95% CI 0.83 to 1.19, 8 RCTs, n=870, I^2=22%）, implantation （RR 1.07, 95% CI 0.83 to 1.39, 4 RCTs, n=1359, I^2=0%）, miscarriage （RR 1.13, 95% CI 0.66 to 1.94, 2 RCTs, n=116, I^2=0%） and multiple pregnancy （RR 0.89, 95% CI 0.31 to 2.52, 1 RCT, n=97,I^2=not applicable） between the treatment group and control group. No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses. Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Intrafollicular Soluble RAGE Benefits Embryo Development and Predicts Clinical Pregnancy in Infertile Patients of Advanced Maternal Age Undergoing In Vitro Fertilization

Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.

Effect of Progestin-primed Ovarian Stimulation Protocol on Outcomes of Aged Infertile Women Who Failed to Get Pregnant in the First IVF/ ICSI Cycle： A Self-controlled Study

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol （PPOS） in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn＇t get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol （non-PPOS group）, and underwent PPOS protocol （PPOS group） in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer （FET） in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone （bFSH）, antral follicle count （AFC）, duration and total dosage of gonadotropin （Gn）, number of oocytes retrieved, intracytoplasmic sperm injection （ICSI） rate, fertilization rate, and cycle cancellation rate between the two groups （P〉0.05）. However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group （P〈0.05）. By the end of April 2017, 62 FET cycles were conducted in PPOS group. The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%, respectively. In conclusion, PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ ICSI-ET cycles.

Ethical dilemma of colorectal screening: What age should a screening colonoscopy start and stop?

Many advanced age patients who are diagnosed with colorectal cancer are often not offered surgical treatment due to presumed high risks of the procedure.While there is data to support surgical treatment of colorectal cancer in advanced age patients,screening colonoscopy is not currently recommended for patients older than 85 years.Moreover,recent studies concluded that the incidence of colorectal cancer in patients 80 years and older is increasing.This raises the concern that the current guidelines are withholding screening colonoscopy for healthy elderly patients.Another concern contrary to this would be the new trend of growing incidence of advanced colorectal cancer in the younger patient population.Together they raise the ethical dilemma of how to best utilize colonoscopies as well as surgical intervention,as they are limited resources.

Maternal Fetal Prognosis: Pregnancy and Delivery in Women of 40 Years Old and Over in a Second Reference Hospital in Bamako

Introduction: Late pregnancies are considered a public health problem linked to maternal mortality due to their complications. These risks, which worsen with maternal age, should be better known and taken into account in monitoring these pregnancies. Objective: To evaluate the impact of age on the prevalence of obstetric and neonatal complications among parturients of 40 years old and over. Methodology: This was an 11-year retrospective analytical case control study from January 1, 2007 to December 31, 2017. The study population was female patients of 40 years old or older for cases and female patients younger than 40 years of control case. Results: In total, we collected 640 cases of parturients of 40 years old and over out of a total of 84,234 deliveries during the study period;i.e. a frequency of 0.76%. Spontaneous abortion increased in patients of 40 and over with 8.28%. Hypertension and diabetes were higher of women of 40 and over, 52.65%. Concerning the method of admission: 55% of parturients of 40 and over were referrals. Incidents occurring among women of 40 and over were more pronounced than in control cases. Complications during vaginal delivery, cervical tear, perineal tear, uterine dehiscence and uterine rupture are high in our cases, i.e. 11.88%;3.59%;2.19%;2.66. During our study, depending on the type of delivery, the cesarean rate was much higher among women of 40 and over than among control cases, i.e. 54.22% versus 12.24%. Hemorrhages in the 3rd trimester were the main indications for cesarean section. Hemorrhages in the 3rd trimester were more frequent with women of 40 and over, i.e. 10.47%;5.94% versus 1.74% and 0.42%. As for the different types of malformations in parturients, women under 40 years old fetal malformations were absent in 92.29%, on the other hand they were more frequent in patients with 40 years and over, i.e. a normal frequency of 36.72%. Conclusion: Pregnancy at a late age exposes the elderly patient and the newborn to several risks. During this study, an increase in maternal-fetal morbidity was observed with aged women.

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, roTOR and the NO-cGMP pathway

Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

Pitavastatin attenuates AGEs-induced mitophagy via inhibition of ROS generation in the mitochondria of cardiomyocytes

This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.

How to Predict AGEs Accumulation Slowdown Effect of a Cosmetic Ingredient? Two Steps <i>In-Vitro</i>System for Evaluating the Anti-AGE Impact of a New Blend

Advanced Glycation End-Products (AGEs), play a crucial part in advancing the process of cellular skin aging and its link to chronological age was re-assessed. AGEs accumulation alters cell structure and function of most types of skin cells, affecting skin’s mechanical and physiological properties, following the molecular transformations. Slowdown AGEs accumulation rate in skin, although a potent anti-aging strategy, is difficult and tricky. The lack of working methods for In-Vitro and In-Vitro measuring AGEs level complicates the evaluation and prediction of active ingredients’ ability to affect cellular AGEs accumulation. A two-step In-Vitro systematic screening method is proposed and three different cosmetic active ingredients were selected for its demonstration, using BSA-Glucose and Collagen-Glucose predicting models. Candidates’ effects on AGEs accumulation were evaluated as standalone, and when formulated in a blend. Additionally, the potency of non-invasive auto-fluorescence in-vivo measurement to detect AGEs levels among subjects of different ages was demonstrated. The results are presented in this work and the potential contribution of the proposed system to assist the desired inhibition of AGEs accumulation in skin is discussed.

Successful Treatment of White Lung in Elderly Patients with COVID-19

Novel coronavirus(SARS-CoV-2,hereby known as COVID-19)has the characteristics of rapid variation and multiple variants,which has caused a huge impact on human health worldwide.At the end of 2022,the Omicron variant was widely spread in China,and the patients infected with COVID-19 were mainly concentrated in the elderly over 80 years old and people with serious basic diseases.Pathologically,diffuse lung injury can be seen in the advanced stage of severe and critical diseases,with a large number of inflammatory cells and fibrous mucus exudation,alveolar epithelial cells shedding and necrosis,severe pulmonary edema,hyaline membrane formation,and diffuse ground-glass shadow or consolidation on imaging,which is manifested as“white lung”[1],and its mortality rate has significantly increased.This study reported two cases of elderly patients admitted to the Affiliated Hospital of Hebei University for the treatment of COVID-19.

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

Anesthetic Considerations in a 98-year-old Man with Periprosthetic Femoral Shaft Fracture

A 98-year-old male patient with history of hemiarthroplasty suffered periprosthetic fracture of right femoral shaft and developed acute coronary event in three days after hospitalization.Femoral nerve and lateral femoral cutaneous nerve blocks combined with general anesthesia were implemented for the internal fixation surgery.The recovery was uneventful after discharge.In this case report,we discussed the main considerations of anesthesia specifically for this complicated case.

Close Correlation between Development of MODS during the Initial 72h of Hospitalization and Hospital Mortality in Severe Fever with Thrombocytopenia Syndrome

An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome （MODS） with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the associa- tion between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients （11.76＋2.05） than in survival patients （4.22~1.98） （P〈0.001）. In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score （P〈0.001）. High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients＇ lives.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Trial

Objective:To evalvate efficacy of Qizi Yusi Pills(QYP),a Chinese medicine compound preparation,on in vitro fertilization-embryo transfer(IVF-ET)in women of advanced reproductive age.Methods:This multicenter,randomized,double-blind,placebo-controlled trial was conducted from June 2018 to October2019.A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design,with 62 patients in each group.All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist(GnRH-a)long protocol.As the QYP group,QYP was administered while the control group received placebo.QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval.Both medications were taken orally at doses of 10 g three times each day.The primary outcome was cumulative pregnancy rate,and the secondary outcomes were periodic medication,follicular status,serum hormone and endometrial receptivity.Follow-up continued until 4 weeks after delivery.Maternal and neonatal complications,such as gestational diabetes,were also observed.Results:Overall,119 patients completed the study,60 in the QYP group and 59 in the placebo group.Per protocol(PP)analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group[43.33%(26/60)vs.25.42%(15/59),P=0.040].Additionally,more oocytes were retrieved from the QYP group than those from the placebo group(8.95±3.12 vs.7.85±1.91,P=0.022).Moreover,the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group(11.78±2.27 mm vs.10.68±2.07 mm,P=0.012).Maternal and neonatal complications between the two groups were not significantly different(P>0.05).Intention-to-treat analysis was in line with PP results.Conclusions:QYP can enhance ovarian reserve capacity and ovarian response,and possibly promote endometrial receptivity.QYP effectively improves cumulative pregnancy rates in older patients(≥35 years)undergoing IVF-ET.(Registration No.ChiCTR1800014427).

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age： a prospective study

Background The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age （AMA）. The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome （DS） and compare the trends of choice of screening and amniocentesis among AMA women. Methods A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20~6 weeks. The patients referred were grouped into a screening group （2107 cases） and an amniocentesis group （3297 cases） by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. Results There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54%o （18/2107）. Twenty- five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7,58%0 （25/3297）. No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group （P=0.928）. The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group （1/131.88 vs. 1/23.78）. With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant （P=0.012）. Conclusions The second trimester serum screening age alone to screen for DS. We suggest educating screening and amniocentesis options. in combination with maternal age was more effective than maternal the patients by recommending AMA women be informed of both