Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc^-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

Diabetic nephropathy is a microvascular complication of diabetes. Its etiology involves metabolic disorder-induced endothelial dysfunction. Endothelium-derived nitric oxide (NO) plays an important role in a number of physiological processes, including glomerular filtration and endothelial protection. NO dysregulation is an important pathogenic basis of diabetic nephropathy. Hyperglycemia and dyslipidemia can lead to oxidative stress, chronic inflammation and insulin resistance, thus affecting NO homeostasis regulated by endothelial nitric oxide synthase (eNOS) and a conglomerate of related proteins and factors. The reaction of NO and superoxide (O₂^.-) to form peroxynitrite (ONOO^-) is the most important pathological NO pathway in diabetic nephropathy. ONOO^- is a hyper-reactive oxidant and nitrating agent in vivo which can cause the uncoupling of eNOS. The uncoupled eNOS does not produce NO but produces superoxide. Thus, eNOS uncoupling is a critical contributor of NO dysregulation. Understanding the regulatory mechanism of NO and the effects of various pathological conditions on it could reveal the pathophysiology of diabetic nephropathy, potential drug targets and mechanisms of action. We believe that increasing the stability and activity of eNOS dimers, promoting NO synthesis and increasing NO/ONOO^- ratio could guide the development of drugs to treat diabetic nephropathy. We will illustrate these actions with some clinically used drugs as examples in the present review.
Diabetes Mellitus ; Diabetic Nephropathies/drug therapy* ; Endothelium, Vascular ; Humans ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase Type III/therapeutic use* ; Oxidative Stress ; Peroxynitrous Acid/therapeutic use*

ObjectiveTo investigate the preventive effects of Astragaloside IV （ASIV） on the formation of colonic adenomatous polyps （CAP） in high-fat-fed （HF） mice with adenomatous polyposis mutation （Apc ^Min/+） and its regulation mechanism on serum metabolite disorders. MethodsA total of 24 mice were evenly assigned to Apc ^Min/+ mice group （Con， n=8）， high-fat diet-fed Apc ^Min/+ mice group （HF， n=8）， and ASIV treatment group （HF-ASIV， n=8）. Apc ^Min/+ mice in HF group and HF-ASIV group were given high-fat diet for 8 consecutive weeks to construct CAP mouse model. Meanwhile， Apc ^Min/+ mice in HF-ASIV group were given 50 mg/kg ASIV every other day for 8 weeks. Daily amount of water intake， food intake and body weight of mice in each group were recorded. At the end of the 8th week， mice were sacrificed for serum and the distal and proximal colon. The number of colonic polyps in each group was recorded. Hematoxylin-eosin （H&E） staining was used to observe the morphological changes of the proximal colon. Immunohistochemistry （IHC） was applied to analyze the amount of COX2 positive cells in the proximal colon. The expression levels of IL-1 β and TNFα in intestinal wall were detected by QRT PCR. Non-targeted metabolic profiling of mouse gut by liquid-phase mass spectrometry was used to screen for differential metabolites and perform functional enrichment. ResultsNo mice died in each group during experiment.ASIV effectively reduced the size and the number of the CAPs that accompanied with the downregulation of inflammatory signaling molecules （COX-2， IL-1 β and TNFα）. Alcian blue and lysozyme staining showed ASIV improved the gut epithelium by promoting goblet and Paneth cells population. Significant differences in metabolite OPLS-DA scores between groups were noted （P < 0.001； P = 0.02）. Compared with HF group， 13 differential metabolites in the serum of HF-ASIV group were significantly recalled， and the levels of the metabolites functionally enriched to N-acetyl-α-D-glucosaminyl-diphosphate were significantly increased in the positive and negative ion modes （P < 0.05） ， which was negatively correlated with the number of medium-sized adenomas （P < 0.01）. ConclusionASIV reduced the number of colonic adenomatous polyps in high-fat-fed Apc ^Min/+ mice and was closely associated with reduced intestinal wall inflammation and regulation of serum metabolite N-acetyl-α-D-glucosamine-diphosphate levels.

The first-generation taxanes (including paclitaxel and docetaxel) are widely used for the treatment of various cancers in clinical settings. In the past decade, a series of new-generation taxanes have been developed which are effective in the inhibition of tumor resistance. However, intravenous (i.v.) infusion is still the only route of administration, and may result in serious adverse reactions with respect to the utilization of Cremophor EL or Tween-80 as solvent. Besides, the dosing schedule is also limited. Therefore, oral administration of taxanes is urgently needed to avoid the adverse reactionss and increase dosing frequency. In this review, we first outlined the discovery and development of taxane-based anticancer agents. Furthermore, we summarized the research progress on the oral formulations of taxanes and proposed some thoughts on the future development of oral taxane formulations.

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.
Pharmacognosy ; Plant Roots/genetics* ; Pueraria

Objective To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. Methods A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. Results There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. Conclusion There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

OBJECTIVE: To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO RESULTS: After treatment, FVC%, MVV%, MEF75%, MEF50%, VO CONCLUSION Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.
Electroacupuncture ; Exercise Tolerance ; Forced Expiratory Volume ; Humans ; Pulmonary Disease, Chronic Obstructive/therapy* ; Respiratory Function Tests