Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

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.

OBJECTIVE: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. METHODS: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. RESULTS: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. CONCLUSION Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans ; Child ; Nutritional Status ; Cross-Sectional Studies ; Iodine ; Sodium Chloride, Dietary/analysis* ; China ; Water

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.
Humans ; Child ; Problem Behavior ; COVID-19 ; Autism Spectrum Disorder ; Epidemics

Electroacupuncture treatment of primary insomnia is widely used and with confirmed efficacy. The factors influencing the therapeutic effect of electroacupuncture include waveform selection, treatment frequency, stimulation intensity, stimulation time and acupoint selection. The mechanism of electroacupuncture in treating this disease mainly includes regulating the levels of excitatory neurotransmitters, γ-aminobutyric acid, melatonin and interleukin cytokines.

Objective To establish the GC characteristic choromatogram of Huanglian Shangqing tablets(pills and granules),and to investigate the quality of the medicinal materials(Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae)containing volatile oil in Huanglian Shangqing tablets(pills and granules).Methods Agilient HP-5 capillary column(30 m×0.32 mm,0.25 μm)was used with temperature programming,the split ratio was 5∶1,the split flow was 5 mL·min-1,the injection volume was 1 μL,and the inlet temperature was 250℃.A hydrogen flame ionization detector was used,with the detector temperature of 260℃,and the column flow was 1 mL·min-1.The quality of samples from different manufacturers was evaluated by using the GC characteristic choromatogram of volatile oil and the identification of characteristic peaks,combined with similarity analysis and principal component analysis.Results The characteristic chromatograms of 192 batches of samples from 56 manufacturers were established.The peaks of Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae were identified as α-pinene and β-pinene,menthol and menthone,and pulegone respectively.The GC choromatogram of volatile oil components in Huanglian Shangqing tablets(pills)from different manufacturers were quite different,and some peaks of indicator components in the products from a few manufacturers have missing.Conclusion The established GC characteristic chromatograms can reflect the product quality status and can be used for the quality evaluation and product quality control of Huanglian Shangqing tablets(pills and capsules).Huanglian Shangqing tablets(pills and capsules)from some manufacturers are insufficient in the active ingredients of volatile oil,therefore,the product quality needs to be improved.

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

Objective: The investigate the effects and mechanism of exosomes derived from human umbilical vein endothelial cells (HUVECs) on wound healing in diabetes rabbits. Methods: The experimental research methods were used. The primary vascular endothelial cells (VECs) and human skin fibroblasts (HSFs) were extracted from skin tissue around ulcer by surgical excision of two patients with diabetic ulcer (the male aged 49 years and the female aged 58 years) admitted to Xiangya Third Hospital of Central South University in June 2019. The cells were successfully identified through morphological observation and flow cytometry. The HUVEC exosomes were extracted by ultracentrifugation and identified successfully by morphological observation, particle size detection, and Western blotting detection. Twenty female 3-month-old New Zealand rabbits were taken to create one type 2 diabetic full-thickness skin defect wound respectively on both sides of the back. The wounds were divided into exosomes group and phosphate buffer solution (PBS) group and treated accordingly, with 20 wounds in each group, the time of complete tissue coverage of wound was recorded. On PID 14, hematoxylin-eosin staining or Masson staining was performed to observe angiogenesis or collagen fiber hyperplasia (n=20). The VECs and HSFs were co-cultured with HUVEC exosomes for 24 h to observe the uptake of HUVEC exosomes by the two kinds of cells. The VECs and HSFs were divided to exosome group treated with HUVEC exosomes and PBS group treated with PBS to detect the cell proliferation on 4 d of culture with cell count kit 8, to detect and calculate the cell migration rate at 24 and 48 h after scratch by scratch test, to detect the cell migration number at 24 h of culture with Transwell test, and to detect the mRNA expressions of nuclear factor-erythroid 2-related factor 2 (NRF2) and transcription activating factor 3 (ATF3) by real time fluorescence quantitative reverse transcription polymerase chain reaction. Besides, the number of vascular branches and vascular length were observed in the tube forming experiment after 12 h of culture of VECs (n=3). The VECs and HSFs were taken and divided into PBS group and exosome group treated as before, and NRF2 interference group, ATF3 interference group, and no-load interference group with corresponding gene interference. The proliferation and migration of the two kinds of cells, and angiogenesis of VECs were detected as before (n=3). Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and least significant difference test. Results: The time of complete tissue coverage of wound in exosome group was (17.9±1.9) d, which was significantly shorter than (25.2±2.3) d in PBS group (t=4.54, P<0.05). On PID14, the vascular density of wound in PBS group was significantly lower than that in exosome group (t=10.12, P<0.01), and the collagen fiber hyperplasia was less than that in exosome group. After 24 h of culture, HUVEC exosomes were successfully absorbed by VECs and HSFs. The proliferative activity of HSFs and VECs in exosome group was significantly higher than that in PBS group after 4 d of culture (with t values of 54.73 and 7.05, respectively, P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs (with t values of 3.42 and 11.87, respectively, P<0.05 or P<0.01) and VECs (with t values of 21.42 and 5.49, respectively, P<0.05 or P<0.01) in exosome group were significantly higher than those in PBS group. After 24 h of culture, the migration numbers of VECs and HSFs in exosome group were significantly higher than those in PBS group (with t values of 12.31 and 16.78, respectively, P<0.01). After 12 h of culture, the mRNA expressions of NRF2 in HSFs and VECs in exosome group were significantly higher than those in PBS group (with t values of 7.52 and 5.78, respectively, P<0.05 or P<0.01), and the mRNA expressions of ATF3 were significantly lower than those in PBS group (with t values of 13.44 and 8.99, respectively, P<0.01). After 12 h of culture, the number of vascular branches of VECs in exosome group was significantly more than that in PBS group (t=17.60, P<0.01), and the vascular length was significantly longer than that in PBS group (t=77.30, P<0.01). After 4 d of culture, the proliferation activity of HSFs and VECs in NRF2 interference group was significantly lower than that in PBS group and exosome group (P<0.05 or P<0.01); the proliferation activity of HSFs and VECs in ATF3 interference group was significantly higher than that in PBS group (P<0.05 or P<0.01) and significantly lower than that in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in ATF3 interference group were significantly higher than those in PBS group (P<0.05 or P<0.01) and significantly lower than those in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in NRF2 interference group were significantly lower than those in PBS group and exosome group (P<0.05 or P<0.01). After 24 h of culture, the migration numbers of VECs and HSFs in ATF3 interference group were significantly more than those in PBS group (P<0.05) and significantly less than those in exosome group (P<0.05 or P<0.01); the migration numbers of VECs and HSFs in NRF2 interference group were significantly less than those in PBS group and exosome group (P<0.01). After 12 h of culture, the vascular length and number of branches of VECs in NRF2 interference group were significantly decreased compared with those in PBS group and exosome group (P<0.01); the vascular length and number of branches of VECs in ATF3 interference group were significantly increased compared with those in PBS group (P<0.01) and were significantly decreased compared with those in exosome group (P<0.01). Conclusions: HUVEC exosomes can promote the wound healing of diabetic rabbits by promoting the proliferation and migration of VECs and HSFs, and NRF2 and ATF3 are obviously affected by exosomes in this process, which are the possible targets of exosome action.
Animals ; Female ; Humans ; Male ; Rabbits ; Collagen/metabolism* ; Diabetes Mellitus ; Exosomes/metabolism* ; Human Umbilical Vein Endothelial Cells ; Hyperplasia/metabolism* ; NF-E2-Related Factor 2/metabolism* ; RNA, Messenger/metabolism* ; Ulcer ; Wound Healing ; Middle Aged