1.Antibacterial properties and compatibility of plasma-activated water/bletilla striata polysaccharide composite hydrogel
Wenxue Ren ; Cheng Cheng ; Wei Han ; Taofeng Liu
Acta Universitatis Medicinalis Anhui 2025;60(11):1996-2004
Objective:
To investigate the antibacterial properties and biocompatibility of a novel hydrogel fabricated by integrating plasma-activated water(PAW) and bletilla striata polysaccharide(BSP).
Methods:
The experiments were carried out by dividing the hydrogels into four groups based on their compositions:the deionized water(DW)-carbomer 940(CBM940)-carboxymethyl chitosan(CMCS) hydrogel group(H group),the PAW-CBM940-CMCS hydrogel(PAH) group,the DW-BSP-CBM940-CMCS hydrogel(BSPH) group,and the PAW-BSP-CBM940-CMCS hydrogel(PA/BSPH) group.Physical properties of the hydrogels were evaluated by testing water loss rate and water vapor transmission rate.The content of active substances was determined using a microplate reader and an electron spin resonance spectrometer(ESR).The pH and ORP values were measured using a pH meter and an oxidation-reduction potential(ORP) electrode.The antibacterial mechanism was elucidated by analyzing the integrity of bacterial biofilms.Antibacterial activity was evaluated via the zone of inhibition assay.Cytotoxicity testing was performed using the cell counting kit-8(CCK-8) assay,and combined with the cell scratch assay,to collectively evaluate the effects of the hydrogel on cellular biocompatibility and migration ability.
Results:
The water loss rate and water vapor transmission rate of PA/BSPH hydrogel were (32. 3 ±2. 3)% and (2 228. 2 ±1 81 . 1) g/( m2 ·d) . Compared with the H group hydrogel , the contents of hydrogen peroxide ( H2 O2 ) and hydroxyl radicals ( ·OH) in PAH and PA/BSPH groups significantly increased (P < 0. 05) , and the diameters of inhibition zones significantly enlarged (P < 0. 05) . The cell viability in PAH group significantly decreased (P < 0. 05) . The PA/ BSPH group showed non-toxicity and a higher cell migration rate ( P < 0. 05 ) .
Conclusion
The antibacterial mechanism of the PA/BSPH hydrogel relies on the reactive species H2 O2 and ·OH in PAW. The incorporation of BSP enhances the water retention and breathability of the wound dressing while significantly reducing the cytotoxici- ty of PAW. This modification endows the hydrogel with improved biocompatibility and promotes cell proliferation . The PA/BSPH hydrogel demonstrates clinical potential by offering a novel therapeutic strategy for chronic infected wound management.
2.Efficacy analysis of curative esophagectomy versus definitive chemoradiotherapy in clinical T1bN0M0 thoracic esophageal cancer
Wenxue WEI ; Wenjian YAO ; Chengzhi DING ; Zeheng MA ; Mengbo LIU ; Yijun ZHANG ; Shoulong LU ; Mingbo LIU ; Li WEI
Chinese Journal of Digestive Surgery 2025;24(10):1290-1297
Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.
3.Efficacy analysis of curative esophagectomy versus definitive chemoradiotherapy in clinical T1bN0M0 thoracic esophageal cancer
Wenxue WEI ; Wenjian YAO ; Chengzhi DING ; Zeheng MA ; Mengbo LIU ; Yijun ZHANG ; Shoulong LU ; Mingbo LIU ; Li WEI
Chinese Journal of Digestive Surgery 2025;24(10):1290-1297
Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.
4.A new classification of left apicoposterior segmental bronchus and its clinical significance
Jian LIU ; Li WEI ; Li ZHU ; Shuai HU ; Tian XIA ; Wenxue WEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):92-98
Objective To analyze a new classification of the left apicoposterior segmental bronchus and summarize its clinical significance. Methods We accessed the computed tomography imaging data of the inpatients treated in the Department of Thoracic Surgery, Henan Provincial People's Hospital between January and November 2021. We observed and classified the branching pattern of the left apicoposterior segmental bronchus (B1+2) using three-dimensional computed tomography bronchography and angiography (3D-CTBA) technique. And we filtered out the patients who underwent thoracoscopic left apicoposterior segmentectomy and analyzed their clinical data retrospectively to summarize the instructing significance of different bronchial classification in the accurate and safe operation of left apicoposterior segmentectomy. Results Finally 240 patients were collected, including 131 males and 109 females with a median age of 51.0 (19.0-77.0) years. The anatomical pattern of the left apicoposterior segmental bronchus was divided into four main types based on the branching pattern of the outer subsegmental bronchi (B1+2c): type Ⅰ 10% (24 patients), type Ⅱ 54% (130 patients) , type Ⅲ 17% (40 patients) , type Ⅳ 18% (43 patients) and other variations 1% (3 patients). Thirty-two patients smoothly underwent thoracoscopic left apicoposterior segmentectomy, including 23 patients of type Ⅰ and type Ⅱ receiving LS1+2 resection, the other 9 patients of type Ⅲ and type Ⅳ receiving LS1+2 resection (3 patients), LS1+2c resection (4 patients) and LS1+2(a+b) resection (2 patients). Conclusion This new classification systematically and concisely elucidates the branching characteristics of the left apicoposterior bronchus. Different branching types are instructive to the left apicoposterior segmentectomy.
5.Analysis of early acute gastrointestinal injury and its influencing factors in patients with extracorporeal membrane oxygenation
Wenxue JIANG ; Chunxi PAN ; Yanlin WEI ; Qiao WEI ; Chi WANG ; Mingyu PEI ; Liwen LYU
Chinese Journal of Emergency Medicine 2024;33(2):210-214
Objective:To investigate the acute gastrointestinal injury (AGI) in patients with extracorporeal membrane oxygenation (ECMO) at the early stage of operation and its influencing factors.Methods:A total of 70 patients with ECMO who were hospitalized in the Emergency Care Unit of Guangxi Zhuang Autonomous Region People's Hospital from September 2020 to December 2021 were retrospectively analyzed, and a total of 70 patients with ECMO who were hospitalized in the emergency care unit of Guangxi Zhuang Autonomous Region People's Hospital from September 2020 to December 2021 were retrospectively analyzed. According to the 2012 guidelines of the European Society of Intensive Care Medicine on the classification of acute gastrointestinal injury in critically ill patients, the patients were divided into AGI group and non-AGI group. The incidence of acute gastrointestinal injury in the early stage was statistically analyzed, and the results of blood gas analysis during ECMO loading and ECMO parameters, hemodynamic indexes and biochemical indexes after ECMO transfer were statistically analyzed. To explore the influencing factors and independent risk factors of AGI in the early stage. In addition, 70 patients were divided into successful group and non-successful group according to whether they were successfully withdrawn. The occurrence of acute gastrointestinal injury between the two groups was compared, and the effect of acute gastrointestinal injury on ECMO patients was analyzed.Results:Among the 70 ECMO patients, the incidence of early AGI was 71.43% (50 cases), and the components of AGI Ⅰ, Ⅱ, Ⅲ and Ⅳ were 18.57% (13 cases), 41.43% (29 cases), 11.43% (8 cases) and 0% (0 cases), respectively. ① Univariate analysis showed that systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), vasoactive drug index (VIS), pH, lactic acid and BMI were significantly different between AGI group and non-AGI group when ECMO was used ( P < 0.05). Logistic binary regression analysis showed that BMI was an independent risk factor for early AGI in ECMO patients (ROC area 0.657, 95% confidence interval 0.522-0.791 ( P < 0.05), and Yoden index 0.15). (3) The AGI composition ratio of the unsuccessful group was higher than that of the unsuccessful group ( P < 0.05). Conclusions:Patients with ECMO have a high incidence of AGI in the early stage, mainly occurring in grade I and Ⅱ. Systolic blood pressure, diastolic blood pressure, MAP, VIS, pH, lactic acid and BMI when ECMO is put on are influential factors for the early development of AGI in ECMO patients, among which BMI is an independent risk factor for the early development of AGI in ECMO patients. The occurrence of AGI reduces the probability of successful withdrawal in ECMO patients.
6.Independent risk factors for renal function non-recovery at 28 days after ECMO initiation among patients receiving ECMO complicated with acute kidney injury
Qiao WEI ; Yanlin WEI ; Mingyu PEI ; Wenxue JIANG ; Chi WANG ; Liwen LYU
Chinese Journal of Emergency Medicine 2024;33(3):317-323
Objective:To investigate the recovery of renal function and its influencing factors in patients receiving extracorporeal membrane oxygenation (ECMO) support and complicated with acute kidney injury(AKI).Methods:This was a retrospective observational study. The clinical data of patients with ECMO support and AKI admitted to the Emergency intensive care unit of the People's Hospital of Guangxi Zhuang Autonomous Region from October 2019 to December 2021 were collected. The patients were divided into renal function recovery group and renal function non-recovery group according to the recovery of renal function after 28 days of ECMO. With renal function non-recovery at 28 days as the end point of the study, and the variables with significant differences in baseline were selected for stepwise backward regression to determine the independent risk factors. The receiver operator characteristic (ROC) curve was drawn, and the area under the curve (AUC) was used to evaluate the diagnostic value of independent risk factors.Results:A total of 40 patients were enrolled, of which 28 patients (70%) had recovery of renal function, and 12 patients (30%) did not have recovery of renal function. Stepwise backward multivariate logistic regression analysis showed that lactate level at ECMO initiation was an independent risk factor for non-recovery of renal function ( OR = 1.380, 95% CI: 1.096-1.738, P = 0.006). The ROC curve showed that the AUC and 95% CI were 0.863 (0.751-0.975), the sensitivity was 100%, and the specificity was 75%. Conclusion:Lactate level at ECMO initiation was an independent risk factor for non-recovery of renal function on 28 days after ECMO initiation among patients undergoing ECMO support complicated with AKI. Lactate has a high predictive value for the non-recovery of renal function.
7.Clinical features and initial outcomes in elderly patients with idiopathic membranous nephropathy
Jinxiu LIANG ; Fangxiao XIA ; Wenke HAO ; Wenxue HU ; Yanhua WU ; Feng YU ; Zhi ZHAO ; Wei LIU
Chinese Journal of Geriatrics 2024;43(2):168-174
Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.
8.Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes
Yibo LEI ; Shuping SUN ; Lu MAO ; Hongen XU ; Wenxue TANG ; Zhaoyu PAN ; Wei LU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(12):1191-1197
Objective:To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness.Methods:Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method.Results:The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband′s mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion:This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.
9.Branchio-oto-renal syndrome or branchio-oto syndrome: the clinical and genetic analysis in five Chinese families
Haifeng FENG ; Hong′en XU ; Bei CHEN ; Shuping SUN ; Beiping ZENG ; Wenxue TANG ; Wei LU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(12):1433-1441
Objective:To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients.Methods:Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient′s clinical results, the appropriate interventions were recommended and implemented.Results:Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions:Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.
10.Effects of bisphenol A exposure at different circadian time on hepatic lipid metabolism in mice
Yan ZHANG ; Min WANG ; Mengya ZHOU ; Zhitian LU ; Xudong LI ; Huihong ZHANG ; Fan WU ; Runxuan ZHUANG ; Zhini HE ; Wenxue LI ; Guangyu YANG ; Wei ZHU ; Bo ZHANG
Journal of Environmental and Occupational Medicine 2022;39(12):1336-1342
Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg−1·d−1) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg−1·d−1 BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg−1·d−1 BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.


Result Analysis
Print
Save
E-mail