19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

Pancreatic polypeptide(PP),a pancreatic hormone containing 36 amino acids,plays impor-tant roles in the diagnosis and evaluation of pancreatic function,injury and diseases.In this study,a phage nanobody library against PP was constructed to screen specific PP nanobodies,which would be used to evaluate whether they have binding activity with PP antigen.After PP antigen with high purity was prepared by prokaryotic expression system,it was used to immunize alpaca to construct the nanobody li-brary against PP with high storage capacity and high abundance,from which 8 strains of PP nanobodies were obtained by phage display.One of nanobody strain(PP-VHH)was selected to be expressed in a prokaryotic expression system,which was induced overnight by IPTG.After purification and identifica-tion,the antigen-antibody binding activity and PP level in serum were detected by indirect ELISA and Sandwich ELISA methods,respectively.The results showed that PP-VHH had binding activity with PP,which could be used to detect PP in chicken and human serum.The Sandwich ELISA methods with R2 of the fitting curve 0.9868 could be used to detect PP concentrations of 48-55 pg/mL in the serum of chick-ens,while the concentrations of PP in human serum varied significantly.In summary,PP-VHH screened from nanobody library against PP could detect PP in serum,which would supply the basis for evaluation of abnormal pancreatic function and diagnosis of relative disease.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Objective To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation(NIV)failure in very low birth weight infants(VLBWI)with gestational age<32 weeks.Methods A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit(NICU)in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted.Based on the outcomes of initial NIV,the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis.Results A total of 817 infants were included,with 453 males(55.4%)and 139 failures(17.0%).The failure group had lower gestational age,birth weight,and 1-minute and 5-minute Apgar scores compared to the successful group(P<0.05).The failure group also had a higher proportion of respiratory distress syndrome(RDS)diagnosed upon NICU admission,higher maximum positive end-expiratory pressure during NIV,and higher percentages of reaching the required maximum fraction of inspired oxygen(FiO2)≥30%,≥35%,and≥40%throughout the initial NIV process compared to the successful group(P<0.05).Gestational age(OR=0.671,95%CI:0.581-0.772),RDS(OR=1.955,95%CI:1.181-3.366),and FiO2≥30%(OR=2.053,95%CI:1.106-4.044)were identified as risk factors for initial NIV failure in these infants with gestational age<32 weeks(P<0.05).The failure group had higher incidences of complications such as pulmonary infections,pneumothorax,retinopathy of prematurity,moderate to severe bronchopulmonary dysplasia,and severe intraventricular hemorrhage during hospitalization,as well as longer hospital stays and higher total costs compared to the successful group(P<0.05).Conclusions Smaller gestational age,a diagnosis of RDS in the NICU,and achieving a maximum FiO2≥30%during the initial NIV process are risk factors for initial NIV failure in infants with gestational age<32 weeks.Initial NIV failure significantly increases the risk of adverse outcomes in this population.

Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2％ collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80％-90％ at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.

Objective:To explore the feasibility and effective methods of obtaining immature oocytes during laparoscopic ovarian tissue resection in female tumor patients, aiming at oocytes freezing matured in vitro for fertility preservation. Methods:Retrospective analysis was made on the general data, surgical methods and postoperative follow-up data of 22 tumor patients who underwent laparoscopic ovarian tissue resection at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from November 2015 to April 2022. The study group included 14 patients who simultaneously obtained in vitro maturation (IVM) of immature eggs during laparoscopy. Control group included 8 patients who only underwent cortical resection. The operation time, the amount of bleeding, the number of frozen cortex and other data of the two groups were analyzed to evaluate the application value and safety of this method. Furtherly, the study group was divided into two subgroups, the transvaginal egg retrieval subgroup (10 patients) and the translaparoscopic egg retrieval subgroup (4 patients), according to the method of different methods used for egg retrieval. The time of surgery, the number of eggs obtained and the number of frozen cortices were analyzed in both subgroups to evaluate the efficiency of the different methods of egg retrieval. All 22 patients were followed up annually after surgery, analyzing the information of tumor treatment, menstrual status, and if possible, pelvic ultrasound and sex hormone levels, recording ovarian function after tumor treatment in these patients and providing hormone replacement therapy (HRT) within the indications. Results:There were no statistically significant differences between the study group and control group in terms of age, duration of disease, anti-Müllerian hormone (AMH) level, and the number of frozen cortices. But the number of basal sinus follicles (19.71±6.04), procedure time [(68.07±17.35) min], and bleeding volume [9.0 (5.0,10.5) mL] in the study group were higher than those in control group with statistically significant differences [9.25±3.15, P<0.001; (44.25±16.97) min, P=0.005; 3.5 (2.0, 5.0) mL, P=0.001]. In the transvaginal egg retrieval subgroup, the number of oocytes obtained [15.5 (11.0, 21.0)] and age [(27.00±2.94) years] were significantly higher than those in the translaparoscopic egg retrieval subgroup [4.0 (0.8, 10.3), P=0.028;(15.75±2.22) years, P<0.001], while no statistically significant differences were observed between the two subgroups in the number of sinus follicles, time to surgery, and number of frozen cortices. All 7 patients who underwent hematopoietic stem cell transplantation (HSCT) had amenorrhea after discharge, and were given HRT after disease remission, and their physical development and quality of life were maintained and improved. Conclusion:Young oncology patients who underwent ovarian cortical resection with simultaneous acquisition of immature eggs, in vitro matured oocytes freezing increased the chance of fertility preservation. The efficiency of transvaginal acquisition of immature oocytes was higher; the rate of amenorrhea after HSCT was high, and HRT could improve the quality of life of patients.

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.
Humans ; Infant, Newborn ; Male ; Citrulline ; Electroencephalography ; Hyperammonemia ; Ornithine Carbamoyltransferase Deficiency Disease/therapy* ; Seizures

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*