Non-invasive prenatal testing (NIPT) based on fetal free DNA is a non-invasive technique to screen for common fetal aneuploidies by analyzing cell-free fetal DNA (cffDNA) in the peripheral blood of pregnant women. This technique has opened a new era of prenatal screening for its high safety and reliability. In recent years, it has been shown that NIPT can not only screen for fetal aneuploidies, but may also reveal maternal genomic abnormalities. The incidental detection of maternal tumors has aroused widespread concern in the clinical settings. The aim of this review is to systematically summarize the research progress of NIPT technique in incidental detection of maternal tumors, and to discuss its clinical significance, technical challenges, and future development direction. It has been found that multiple chromosome aneuploidies (MCAs) in NIPT detection is one of the important biomarkers suggesting occult maternal malignant tumors. In this paper, the relevant progress of NIPT technique in the incidental discovery of maternal tumors were reviewed in order to provide a reference for individualized and standardized application of NIPT technique in maternal health monitoring.
Humans ; Female ; Pregnancy ; Cell-Free Nucleic Acids/blood* ; Prenatal Diagnosis/methods* ; Incidental Findings ; Neoplasms/genetics* ; Noninvasive Prenatal Testing/methods* ; Aneuploidy ; Fetus/metabolism*

Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic (ANT) application and affect gene expression. In this study, we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate (GLY), two ANTs, and one anticoccidial drug (AD). A total of 260 Ross 308 broilers aged 1‍-‍40 d were divided into the following four groups of 65 birds each: control group, which was fed the main diet (MD), and three experimental groups, which were fed MD supplemented with GLY, GLY+ANTs (enrofloxacin and colistin methanesulfonate), and GLY+AD (ammonium maduramicin), respectively. The results showed that the addition of GLY, GLY+ANTs, and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance. In particular, genes related to inflammation and apoptosis (interleukin 6 (IL6), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 6 (CASP6)) were downregulated by up to 99.1%, and those related to antioxidant protection (catalase (CAT), superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (PRDX6)) by up to 98.6%, compared to controls. There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups, and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood. The changes revealed in gene expression and blood indices in response to GLY, ANTs, and AD provide insights into the possible mechanisms of action of these agents at the molecular level. Specifically, these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY, GLY+ANTs, and GLY+AD in broilers.
Animals ; Glyphosate ; Glycine/administration & dosage* ; Chickens/blood* ; Pancreas/metabolism* ; Anti-Bacterial Agents/pharmacology* ; Animal Feed ; Gene Expression/drug effects* ; Herbicides

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.
Humans ; Drug Delivery Systems/methods* ; Ischemic Stroke/drug therapy* ; Animals ; Blood-Brain Barrier/metabolism* ; Stroke/drug therapy*

BACKGROUND: Studies on the impact of blood glucose indicators on metabolism remain relatively scarce. The aim of this study was to investigate the associations between blood glucose indicators and metabolic disorders in China. METHODS: Data were from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE survey), which randomly selected 31 cities from 31 provinces in the Chinese mainland. A total of 68,383 participants without preexisting diabetes and have complete data on blood glucose, lipids, and blood pressure were included in the analysis. The diabetic population was divided into seven groups based on different types of elevated blood glucose levels, including fasting plasma glucose (FPG), postprandial glucose (PPG), and hemoglobin A1c (HbA1c): FPG ≥7 mmol/L; PPG ≥11.1 mmol/L; HbA1c ≥6.5%; FPG ≥7 mmol/L and PPG ≥11.1 mmol/L; FPG ≥7 mmol/L and HbA1c ≥6.5%; PPG ≥11.1 mmol/L and HbA1c ≥6.5%; FPG ≥7 mmol/L, PPG ≥11.1 mmol/L, and HbA1c ≥6.5%. The effects of each blood glucose indicator on metabolism were investigated separately. Weighted calculation was applied during the analysis, with the weighting coefficient based on the number of people corresponding to the population characteristics of each sample in the 2010 Chinese Census. A logistic regression model with restricted cubic splines (RCS) was employed to characterize the nonlinear associations of age and body mass index (BMI) with the risk of diabetes subtypes defined by distinct blood glucose indicators elevations, as well as the relationships between different blood glucose indicators (FPG, PPG, HbA1c) and the risk of metabolic disorders such as hypertension, hypertriglyceridemia, hypercholesterolemia, high low-density lipoprotein cholesterol (high LDL-C) and low high-density lipoprotein cholesterol (low HDL-C). RESULTS: Among individuals with diabetes, elevated PPG alone was the most common abnormality, affecting 26.96% (1382/5127) of the population. Among the seven groups with only one elevated blood glucose indicator, individuals with elevated PPG alone exhibited the highest mean levels of triglycerides (TG) at 2.11 mmol/L (95% confidence interval [CI]: 1.97-2.25 mmol/L, P = 0.004), total cholesterol (TC) at 5.26 mmol/L (95% CI: 5.18-5.33 mmol/L, P <0.001), and low-density lipoprotein cholesterol (LDL-C) at 3.12 mmol/L, (95% CI: 3.06-3.19 mmol/L, P = 0.001). Individuals with elevated PPG alone showed a high prevalence of hypertension (806/1382, 58.32%), hypertriglyceridemia (676/1382, 48.91%), hypercholesterolemia (694/1382, 50.22%), High LDL-C (525/1382, 37.94%), and Low HDL-C (364/1382, 26.34%). The association of age and BMI with the risk of diabetes revealed that the older the patient, the steeper the RCS curve for the odds ratio (OR) of diabetes with elevated PPG alone (age = 60, OR = 2.79, 95% CI [2.49-3.12], P <0.01). Similarly, as BMI increased, the RCS curve for the OR of diabetes with elevated HbA1c alone also steepened (BMI = 35, OR = 3.75, 95% CI [3.23-4.35], P <0.001). Additionally, the RCS yielded a positive association between blood glucose indicators and metabolic diseases risk. In individuals with diabetes, RCS for both the ORs of metabolic diseases (hypertension, hypertriglyceridemia, hypercholesterolemia, high LDL-C, low HDL-C) and the levels of metabolic indicators (TG, TC, LDL-C, HDL-C) revealed some inflection points within the ranges of FPG 5-6 mmol/L, PPG 6-8 mmol/L, and HbA1c 5.5-6.0%. CONCLUSIONS PPG is more closely related to metabolic disorders than FPG and HbA1c in people with diabetes. For patients with diabetes and metabolic disorders, it may be necessary to monitor blood glucose fluctuations within specific ranges (FPG 5-6 mmol/L, PPG 6-8 mmol/L, and HbA1c 5.5-6.0%).
Humans ; Female ; Cross-Sectional Studies ; Male ; Blood Glucose/metabolism* ; Middle Aged ; Glycated Hemoglobin/metabolism* ; Adult ; Metabolic Diseases/epidemiology* ; Aged ; China ; Diabetes Mellitus/blood* ; East Asian People

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

Diabetes mellitus (DM) is a major global health issue, with glycated hemoglobin levels serving as the gold standard for evaluating glucose level control in DM patients. However, it has limitations in reflecting glucose oscillations (i.e. glycemic variability, GV). Increasing evidence suggests that GV is closely related to the progression of diabetes complications and patient prognosis. As people realize the importance of avoiding hypoglycemia while achieving target glycated hemoglobin levels in treatment, the clinical significance of GV becomes more obvious. This article systematically reviewed the concept and connotation of GV, summarized the latest research on its role in the complications of diabetes, and revealed the biochemical and pathophysiological abnormalities caused by excessive glycemic oscillation, aiming to provide a theoretical basis for the risk warning and early intervention of DM patients.
Humans ; Blood Glucose/metabolism* ; Diabetes Complications/physiopathology* ; Glycated Hemoglobin/metabolism* ; Hypoglycemia ; Diabetes Mellitus, Type 2/complications*

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a significant cause of disease morbidity. One-third of patients with ASUC are steroid refractory. Rescue therapy may not successfully induce remission, necessitating colectomy. We aimed to identify predictors of rescue therapy and colectomy in ASUC assessed within 24 h of admission for early risk stratification. METHODS: We conducted a retrospective cohort study of 58 admissions for ASUC among 47 patients from August 2002 to January 2022. Serum biomarkers assessed were measured on admission. Primary outcomes were the need for rescue therapy during the same admission and colectomy within 1 year of admission. RESULTS: Rescue therapy (all with infliximab) was given in 20 (34.5%) of the admissions. Colectomy was done within 1 year for nine (15.5%) of the admissions. An elevated C-reactive protein (CRP) of >30 mg/L (relative risk [RR] 1.63), a CRP-albumin ratio of >0.85 (RR 1.63), and a composite factor of both CRP > 30 mg/L and age ≥60 years (RR 2.37) were significantly associated with the need for rescue therapy. Hypoalbuminaemia ≤ 25 g/L (RR 4.35) and the use of biologics at presentation (RR 1.54) were significantly associated with colectomy within 1 year of admission, while a CRP of ≥ 80 mg/L was a significant protective factor (RR 0.70). CONCLUSION Patients with ASUC who have elevated CRP or CRP-albumin ratio on admission should be considered at risk for steroid-refractory disease. Those with hypoalbuminaemia on admission and using biologics at presentation are more likely to require colectomy in the first year after admission for ASUC.
Humans ; Colitis, Ulcerative/therapy* ; Colectomy ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult ; C-Reactive Protein/metabolism* ; Infliximab/therapeutic use* ; Biomarkers/blood* ; Acute Disease ; Aged ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function. METHODS: Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg^-1•d^-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry. RESULTS: Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01). CONCLUSION "Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals ; Male ; Mice ; Apoptosis ; Acupuncture Therapy ; Mitochondria/metabolism* ; Asthenozoospermia/genetics* ; Humans ; Testis/metabolism* ; Mice, Inbred C57BL ; Spermatozoa/metabolism* ; Acupuncture Points ; Sperm Motility ; Testosterone/blood* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Caspase 3/genetics* ; Follicle Stimulating Hormone/blood* ; Reproduction ; Cytochromes c/genetics* ; bcl-2-Associated X Protein/genetics* ; Apoptotic Protease-Activating Factor 1/genetics*

OBJECTIVE: To observe the efficacy of "Biaoben acupoint compatibility" moxibustion for abdominal obesity and its effect on blood lipid, lipid accumulation product (LAP) and cardiometabolic index (CMI). METHODS: A total of 150 patients with abdominal obesity were randomly divided into an observation group (75 cases, 5 cases dropped out) and a control group (75 cases, 6 cases dropped out). The control group received lifestyle guidance. The observation group received "Biaoben acupoint compatibility" moxibustion at Zhongwan (CV12), Guanyuan (CV4) and bilateral Tianshu (ST25), Zusanli (ST36) on the basis of the control group, 20 min each time, once every other day, 3 times a week for 8 weeks. Before and after treatment, the waist circumference, hip circumference, weight, body mass index (BMI) were observed, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the LAP and CMI were calculated in the two groups. RESULTS: After treatment, the waist circumference, weight and BMI were decreased compared with those before treatment in both groups (P<0.05), the changes of the above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the hip circumference, TC level, TG level, LAP and CMI in the observation group were decreased compared with those before treatment (P<0.05), the HDL-C level was increased compared with that before treatment (P<0.05)；the changes of the TC level, TG level, LAP, CMI and HDL-C level in the observation group were larger than those in the control group (P<0.05). CONCLUSION "Biaoben acupoint compatibility" moxibustion can reduce the degree of obesity in patients with abdominal obesity, and improve blood lipid and reduce lipid accumulation.
Humans ; Acupuncture Points ; Moxibustion ; Male ; Female ; Middle Aged ; Obesity, Abdominal/blood* ; Adult ; Lipids/blood* ; Lipid Metabolism ; Triglycerides/blood* ; Young Adult ; Treatment Outcome ; Aged