OBJECTIVE To explore the applicablity of 'BlueScreen HC'(BSHC),a high throughput genotoxicity screening system based on human growth arrest and DNA damage inducible 45α(GADD45α)gene,in detecting the genotoxicity of migrants mixtures from food contact materials(FCM).METHODS The 2000 bp sequence upstream of the open reading frame of human GADD45α gene was used as the promoter to construct the lentiviral plasmid pEZX-LvPG04,which was double labeled by purinamycin and Gausluciferase(Gluc),and the lentiviral plasmid was infected with human lymphoblastocyte TK6 to obtain a stable transmutation cell line TK6-Gluc.Methyl methylate(MMS)at concentrations of 0,1.56,3.13,6.25,12.5,25.0 and 50.0 mg·L-1 was selected as the genotoxin without liver S9,cyclophosphamide(CTX)0,0.78,1.56,3.13,6.25,12.5,25.0 mg·L-1 was selected as the pre-genotoxin with liver S9,and dimethyl sulfoxide(DMSO)0,0.35,0.69,1.38,2.75,5.5 and 11.0 g·L-1 was selected as the non-genotoxin.The constructed BSHC was verified with the above known genetic positive and negative substance respectively.Polybutyleneadipate-co-terephthalate(MS/PBAT)was tested using 4% (V/V)acetic acid,and 10%,20%,50% and 95% (V/V)ethanol as food simulants at 40℃for 24 hours to obtain 5 multi-component migrants of MS/PBAT that were obtained by using DMSO as a solvent.TK6-Gluc cells were treated with 5 multi-component migrants of MS/PBAT at concentrations of 0,0.38,0.76,1.53,3.05,6.10 and 12.20 g·L-1 with or without liver S9.Cells were treated without liver S9 for 48 h.Cells treated with liver S9-mix were incubated for 3 h at a final concen-tration of 1% (V/V)liver S9 before being washed and re-suspended in fresh recovery media for another 45 h.After exposure,the cell viability was detected using the CCK-8 cell activity kit,and the Gluc Lumi-nescence in the medium was detected with Secrete-PairTM Gaussia Luciferase Assay Kit.In addition,the mutagenicity on Salmonella typhimurium TA98 and TA100 was detected by micro-fluctuation Ames test with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1.The in vitro mammalian cell chromosome aberration test was performed on CHL cells with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1 to detect the chromosomal aberration.The results of genotoxicity were compared with those of BSHC.RESULTS The lowest effect centra-tion(LEC;<80% relative cell viability)and the coytotoxicity(<30% relative cell viability)was defined.A positive genotoxicity result threshold was determined at 1.8-fold relative induction.For the liver S9 protocol,the same process was followed,and the decision threshold derived was 1.5-fold relative Gluc induction.It is considered as genetic substance only when a positive genotoxicity result was reached and there was no cytotoxicity.Compared with the vehicle control group,no genotoxicity was observed at all concentration of DMSO by BSHC.MMS 12.5,25.0 and 50.0 mg·L-1 produced genotoxicity without liver S9 while CTX 6.25,12.5 and 25.0 mg·L-1 produced genotoxicity with liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1,and in 50% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1 without liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups,and no high expression of Gluc was observed.Therefore,none of the 5 multi-component migrants produced genotoxicity without liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1,and in 4% acetic acid migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1 with liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups.No high expression of Gluc was observed.There-fore,none of the 5 multi-component migrants produced genotoxicity with liver S9.In the micro fluctua-tion Ames test,when 5 multi-component migrants of MS/PBAT were treated with concentrations of 3.05 and 12.20 g·L-1 on TA98 and TA100 strains,there was no significant difference in the number of muta-genic positive wells compared with DMSO control group with or without liver S9,indicating that no mutagenic effect was produced.When CHL cells were treated with 5 multi-component migrants of MS/PBAT at concentration of 3.05 and 12.20 g·L-1,compared with DMSO control group,there was no signifi-cant difference in chromosome aberration rate of CHL cells with or without liver S9.CONCLUSION BSHC based on GADD45α gene has been established,which can be used for in vitro genotoxicity eval-uation of migrants mixtures of FCM,but further exploration of its minimum effective concentrations is still needed,and more types of mixtures need to be applied for further validation.

Objective:To explore the characteristics of brain dynamic activity in patients with schizophrenia by using functional magnetic resonance imaging(fMRI).Methods:Forty-three patients with schizophrenia and 31 normal controls were recruited and under fMRI scanning.The Positive and Negative Symptom Scale(PANS)was used to assess the severity of clinical symptoms.The DPABI software were used to compute dReHo and dFC.Granger causality analysis was used to calculate the effective connectivity between the significant brain regions of dReHo and the whole brain.Two sample t-test was performed to compare the difference of dReHo and dFC be-tween patients with schizophrenia and normal controls.Results:The dReHo of left postcentral gyrus(LPG)(P＜0.01,cluster-level FWE corrected)in patients with schizophrenia was decreased.The Dfc was increased between left postcentral and left middle frontal gyrus,left superior medial frontal gyrus,right calcarine,left medial cingulum gyrus,right supplementary motor area(P＜0.01,uncorrected).Compared with normal controls,patients with schiz-ophrenia showed decreased effective connectivity from LPG to right putamen.Conclusion:It suggests that the ab-normal functional activity of the postcentral gyrus mightcontribute to the neural physiopathology in patients with schizophrenia.

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Objective:To evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Chinese rhinoplasty.Methods:A retrospective chart review was conducted for patients who underwent pollybeak correction between January 2021 and December 2022 at the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University. Individualized correction was tailored based on the etiology and severity of the nasal deformity of each patient, involving techniques such as resection of the anterior part of the nasal septum, reconstruction of nasal tip support, reconstruction of the middle part of the nasal vault, and excision of skin in the upper region of the nasal tip. A modified classification system for pollybeak deformity, the supratip fullness rating scale (SFRS), was developed to evaluate supratip fullness (0-3 points, with higher scores indicating more apparent deformity). The patients aesthetic outcomes were assessed by surgeons using the visual analogue scale (VAS) (0-10 points, with higher scores indicating more apparent deformity), and patient self-assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (0-100 points, with higher scores indicating higher satisfaction). The measurement data of normal distribution was expressed as Mean±SD and analyzed by paired t-test; the measurement data of non-normal distribution was expressed as M( Q1, Q3) and analyzed by Wilcoxon signed rank test. Results:In a cohort study of 53 rhinoplasty patients (7 male, 46 female; age range 19-45 years, mean 29 years), comprising 15 primary and 38 secondary surgeries, nasal tip deformities were evaluated. Deformities were classified as mild (5 cases), moderate (25 cases), and severe (23 cases). Over a follow-up period of 6-17 months (mean 9.5 months), significant aesthetic improvements in the nasal tip region were observed. The SFRS scores decreased from 2(2, 3) preoperatively to 0(0, 0) postoperatively ( Z = -6.58, P < 0.001), and VAS scores decreased from 7.47±1.73 to 1.79±1.67 ( t = -25.61, P < 0.001). High patient satisfaction was indicated by a mean ROE score of 82.45±11.55. No significant complications, such as nasal tip ptosis, skin necrosis, or scar hyperplasia, were reported. Conclusion:Selecting an appropriate surgical method based on the severity and cause of pollybeak deformity can achieve satisfactory outcomes. Post-operative patients exhibit significant aesthetic improvement in the upper nasal tip area, resulting in high patient satisfaction.

Objective:To investigate the surgical effect of pedicled upper lip mucosal flap in repairing nasal septal mucosal defects after rhinoplasty.Methods:A retrospective analysis was performed from January 2016 to October 2022, the clinical data of patients with nasal septal mucosal defects after rhinoplasty were collected in the Department of Plastic and Aesthetic (Burn) Surgery at the Second Xiangya Hospital of Central South University. The pedicled upper lip mucosal flap was utilized for repair based on the patient’s medical history and wound condition. The pedicle of the flap was designed 1 cm adjacent to the frenulum of the upper lip, and an appropriate flap was incised based on the size of the wound, with dissection performed up to the superficial layer of the orbicularis oris muscle. The dissection establishes an upper lip tunnel that connects the gingival-buccal groove to the nasal cavity. The pedicled upper lip mucosal flap was elevated and transposed into the nasal cavity via the upper lip tunnel. The position of the flap was adjusted to ensure complete coverage and fixation of the nasal septal defect wound using 5-0 absorbable suture. The visual analogue scale (VAS) and the nasal obstruction symptom evaluation (NOSE) scale were utilized to facilitate patients’ satisfaction evaluation and assessment of nasal obstruction symptoms before surgery and at 6 months post-surgery. The VAS total score was 10 points, with higher scores indicating greater levels of patient satisfaction. The NOSE scale comprises of 5 items, each assigned a score ranging from 0 to 4, denoting absence of symptoms, very mild presence, moderate intensity, relatively severe manifestation, and highly severe indication respectively. The measurement data of VAS and NOSE scores before surgery and at 6 months post-surgery was expressed by Mean±SD, using paired t-test. The score distribution of the NOSE scale was represented by the number of cases, using Mann-Whitney U test. Results:The study included a total of 15 female patients, with an average age of (27.6±2.9) years (ranging from 23 to 33 years). Eleven cases presented with preoperative cartilage exposure, and the size of tissue defect ranged from 0.9 cm×0.5 cm to 1.5 cm×0.7 cm. Nine patients had a history of smoking. Skin grafting was performed in 9 patients, while nasal mucosal metastasis was observed in 8 patients. The dimensions of the flap varied from 4.0 cm×1.2 cm to 7.0 cm×1.5 cm. The postoperative recovery was satisfactory, with successful survival of the skin flaps and no occurrences of infection, hematoma, wound dehiscence, or flap necrosis. The average duration of follow-up was (8.2±2.1) months (ranging from 6 to 12 months). The postoperative VAS score (7.73±0.88) was significantly higher compared to the preoperative score (1.86±0.74) ( P<0.01). Additionally, the postoperative NOSE score (4.66±1.71) showed a significant decrease from the preoperative score (10.73±2.68), with a statistically significant difference ( P<0.01). Among them, after surgery items of stuffy or unbreathable nose (2 cases vs. 15 cases), nasal obstruction (1 case vs. 14 cases), and feeling that the nose was not enough to breathe during exercise or exertion (4 cases vs. 14 cases) scored≥2 points were significantly less than those before operation (all P<0.01). Conclusion:The utilization of pedicled upper lip mucosal flap in the reconstruction of severe nasal septal mucosal defects following rhinoplasty has proven to be highly effective. The postoperative satisfaction of patients is remarkably high, the ventilation function exhibits significant improvement, and no severe complications are observed.

Objective:To evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Chinese rhinoplasty.Methods:A retrospective chart review was conducted for patients who underwent pollybeak correction between January 2021 and December 2022 at the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University. Individualized correction was tailored based on the etiology and severity of the nasal deformity of each patient, involving techniques such as resection of the anterior part of the nasal septum, reconstruction of nasal tip support, reconstruction of the middle part of the nasal vault, and excision of skin in the upper region of the nasal tip. A modified classification system for pollybeak deformity, the supratip fullness rating scale (SFRS), was developed to evaluate supratip fullness (0-3 points, with higher scores indicating more apparent deformity). The patients aesthetic outcomes were assessed by surgeons using the visual analogue scale (VAS) (0-10 points, with higher scores indicating more apparent deformity), and patient self-assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (0-100 points, with higher scores indicating higher satisfaction). The measurement data of normal distribution was expressed as Mean±SD and analyzed by paired t-test; the measurement data of non-normal distribution was expressed as M( Q1, Q3) and analyzed by Wilcoxon signed rank test. Results:In a cohort study of 53 rhinoplasty patients (7 male, 46 female; age range 19-45 years, mean 29 years), comprising 15 primary and 38 secondary surgeries, nasal tip deformities were evaluated. Deformities were classified as mild (5 cases), moderate (25 cases), and severe (23 cases). Over a follow-up period of 6-17 months (mean 9.5 months), significant aesthetic improvements in the nasal tip region were observed. The SFRS scores decreased from 2(2, 3) preoperatively to 0(0, 0) postoperatively ( Z = -6.58, P < 0.001), and VAS scores decreased from 7.47±1.73 to 1.79±1.67 ( t = -25.61, P < 0.001). High patient satisfaction was indicated by a mean ROE score of 82.45±11.55. No significant complications, such as nasal tip ptosis, skin necrosis, or scar hyperplasia, were reported. Conclusion:Selecting an appropriate surgical method based on the severity and cause of pollybeak deformity can achieve satisfactory outcomes. Post-operative patients exhibit significant aesthetic improvement in the upper nasal tip area, resulting in high patient satisfaction.

Objective:To investigate the surgical effect of pedicled upper lip mucosal flap in repairing nasal septal mucosal defects after rhinoplasty.Methods:A retrospective analysis was performed from January 2016 to October 2022, the clinical data of patients with nasal septal mucosal defects after rhinoplasty were collected in the Department of Plastic and Aesthetic (Burn) Surgery at the Second Xiangya Hospital of Central South University. The pedicled upper lip mucosal flap was utilized for repair based on the patient’s medical history and wound condition. The pedicle of the flap was designed 1 cm adjacent to the frenulum of the upper lip, and an appropriate flap was incised based on the size of the wound, with dissection performed up to the superficial layer of the orbicularis oris muscle. The dissection establishes an upper lip tunnel that connects the gingival-buccal groove to the nasal cavity. The pedicled upper lip mucosal flap was elevated and transposed into the nasal cavity via the upper lip tunnel. The position of the flap was adjusted to ensure complete coverage and fixation of the nasal septal defect wound using 5-0 absorbable suture. The visual analogue scale (VAS) and the nasal obstruction symptom evaluation (NOSE) scale were utilized to facilitate patients’ satisfaction evaluation and assessment of nasal obstruction symptoms before surgery and at 6 months post-surgery. The VAS total score was 10 points, with higher scores indicating greater levels of patient satisfaction. The NOSE scale comprises of 5 items, each assigned a score ranging from 0 to 4, denoting absence of symptoms, very mild presence, moderate intensity, relatively severe manifestation, and highly severe indication respectively. The measurement data of VAS and NOSE scores before surgery and at 6 months post-surgery was expressed by Mean±SD, using paired t-test. The score distribution of the NOSE scale was represented by the number of cases, using Mann-Whitney U test. Results:The study included a total of 15 female patients, with an average age of (27.6±2.9) years (ranging from 23 to 33 years). Eleven cases presented with preoperative cartilage exposure, and the size of tissue defect ranged from 0.9 cm×0.5 cm to 1.5 cm×0.7 cm. Nine patients had a history of smoking. Skin grafting was performed in 9 patients, while nasal mucosal metastasis was observed in 8 patients. The dimensions of the flap varied from 4.0 cm×1.2 cm to 7.0 cm×1.5 cm. The postoperative recovery was satisfactory, with successful survival of the skin flaps and no occurrences of infection, hematoma, wound dehiscence, or flap necrosis. The average duration of follow-up was (8.2±2.1) months (ranging from 6 to 12 months). The postoperative VAS score (7.73±0.88) was significantly higher compared to the preoperative score (1.86±0.74) ( P<0.01). Additionally, the postoperative NOSE score (4.66±1.71) showed a significant decrease from the preoperative score (10.73±2.68), with a statistically significant difference ( P<0.01). Among them, after surgery items of stuffy or unbreathable nose (2 cases vs. 15 cases), nasal obstruction (1 case vs. 14 cases), and feeling that the nose was not enough to breathe during exercise or exertion (4 cases vs. 14 cases) scored≥2 points were significantly less than those before operation (all P<0.01). Conclusion:The utilization of pedicled upper lip mucosal flap in the reconstruction of severe nasal septal mucosal defects following rhinoplasty has proven to be highly effective. The postoperative satisfaction of patients is remarkably high, the ventilation function exhibits significant improvement, and no severe complications are observed.

Objective:To investigate the effects of Shenghui Yizhi Decoction on learning and memory ability of SAMP8 mice; To explore its mechanism.Methods:Totally 24 male SAMP8 mice were randomly divided into model group, donepezil hydrochloride group (1 mg/kg) and Shenghui Yizhi Decoction group (15.6 g/kg), with 8 mice in each group, and eight anti rapid aging mice (SAMR1) of the same age and strain were set as the control group. The mice in each group were given corresponding medication or the same volume of distilled water for 90 days. After administration, Morris water maze was used to detect the learning and memory ability and space exploration ability of mice. Immunohistochemistry was used to detect expression of β Amyloid protein 1-42 (Aβ 1-42) in hippocampal. ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Real time PCR was used to detect expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA. Western Blot was used to detect expression of NLRP3, Caspase-1and IL-1β protein. Results:Compared with model group, the spatial exploration ability and memory ability of mice in Shenghui Yizhi Decoction group and donepezil hydrochloride group were improved ( P<0.05, P<0.01), the expression of Aβ 1-42 in hippocampus decreased ( P<0.05, P<0.01), the contents of IL-1β, IL-6 and TNF-α decreased ( P<0.05, P<0.01), and the mRNA and protein expressions of NLRP3, Caspase-1 and IL-1β decreased ( P<0.05, P<0.01). Conclusion:Shenghui Yizhi Decoction can effectively improve the learning and memory ability of SAMP8 mice, and its mechanism may be related to inhibiting the activation of inflammasome and neuroinflammatory response by regulating the NLRP3/ Caspase-1/ IL-1β signaling pathway.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.