Objective To explore the expression characteristics of BAIAP2L1 in cervical cancer (CC) and its regulatory role in tumor cell metastasis. Methods The correlation between BAIAP2L1 expression and clinical prognosis was analyzed by using a public database. GO pathway enrichment and clinicopathological correlation analyses were conducted by employing R language. The effect of BAIAP2L1 knockdown on CC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) were further investigated through gene silencing approaches. Results BAIAP2L1 expression was significantly upregulated in CC tissues (P_adj <0.001) and it was identified as an independent risk factor for patient mortality (HR=2.808, P=0.03). Elevated BAIAP2L1 levels showed significant correlations with poor overall survival, advanced T/N stage, recurrence, and metastasis (all P<0.05). Functional enrichment analysis revealed its involvement in tumor metastasis-related pathways. The knockdown of BAIAP2L1 significantly attenuated CC cell proliferation, invasion, and migration and suppressed key EMT processes (all P<0.05). Conclusion BAIAP2L1 is overexpressed in CC tissues and associated with patient prognosis and metastasis. The targeted inhibition of BAIAP2L1 can effectively curb tumor progression.

Objective:To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults.Methods:In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1, Q3) for TSH, T 3, and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI:-15.17%, -4.36%) and 11.14% (95% CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion:Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

Objective:To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults.Methods:In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1, Q3) for TSH, T 3, and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI:-15.17%, -4.36%) and 11.14% (95% CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion:Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

Objective To investigate the clinical efficacy of dot matrix laser combined with subcutaneous separation in the treatment of depressed acne scar.Methods A total of 86 patients with depressed acne scar admitted to the Second Affiliated Hospital of Nanchang University from February 2022 to August 2023 were selected and divided into dot matrix group and combined group according to random number table method,with 43 cases in each group.The patients in dot matrix group were treated with dot matrix laser,and the patients in combined group were treated with dot matrix laser combined with subcutaneous separation.The visual analogue scale(VAS)score,echelle d'evaluation clinique des cicatrices d'acne(ECCA)score,pigmentation area,scar area,treatment satisfaction and adverse reactions were compared between two groups.Results There was no significant difference in VAS scores between two groups after the first treatment and the second treatment(P>0.05).Three months after treatment,the ECCA score of combined group was significantly lower than that of dot matrix group,and the pigmentation area and scar area were significantly smaller than those of dot matrix group(P<0.05).The total satisfaction of patients in combined group was significantly higher than that in dot matrix group(χ2=4.746,P=0.029).There was no significant difference in the occurrence of adverse reactions between two groups(χ2=0.453,P=0.501).Conclusion Dot matrix laser combined with subcutaneous separation in the treatment of depressed acne scar can effectively promote scar repair,reduce skin pigmentation area and scar area,and do not increase pain,with good safety and high patient satisfaction.

BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction.However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein–protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize b-catenin and enhance the intensity of Wnt/b-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.

Objective:To study on performance comparison between clinic digital memory assessment and previously used assessments in dementia risk screening.To compare the performance comparison between Beijing Aging Brain Rejuvenation Initiative(BABRI)Brain Health System's Clinic Digital Memory Detection as study and Alzheimer Disease-8(AD8)and the Brief Community Screening Instrument for Dementia(BCSID)as controls, We calculated and evaluated the accuracy, sensitivity and specificity of screening Mild cognitive impairment(MCI)among these tests.Furthermore, BABRI Brain Health System was used to conduct a large sample brain health examination and early dementia screening to test the validity, adaptability and stability of the evaluation results by BABRI Brain Health System'Clinic Digital Memory Detection.Methods:Dataset 1 contained 669 elderly subjects from five communities in Beijing were recruited according to inclusion and exclusion standard.The diagnosis of MCI was based on the full set of neuropsychological scale and Petersen standard.Dataset 1 was used to compare the discriminant effect of BABRI Brain Health System'Clinic Digital Memory Detection as study versus AD8 and BCSID as controls.The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of each measurement tool were calculated.Then, the receiver operator characteristic(ROC)curve was prepared to compare the discrimination ability of MCI between each measurement tool.While the area under the curve(AUC)of different tools was compared by Wald χ2 test.Dataset 2 contained 284 103 subjects from 16 communities in Beijing, which were used to test the applicability of large sample screening in BABRI Brain Health System. Results:77 patients with MCI were found among 666 people, and incidence rate was 11.56% using the full set of neuropsychological scales in dataset 1.Compared with the results of other tests, the sensitivity of BABRI Brain Health System to correctly distinguish MCI was 0.753, which was close to BCSID, and better than AD8.In addition, BABRI Brain Health System's Youden's index was 0.741 and AUC was 0.905, which suggested that the specificity, positive predictive value, negative predictive value and cognitive domain coverage of MCI screening were generally better in BABRI Brain Health System than in AD8 and BCSID.Finally, the Brain Health Examination results of 284, 000 people in dataset 2 showed that the high-risk detection rate of MCI(8.65%)of the tool for people over 50 years old under a large sample was quite close to the results of dataset 1(8.67%), indicating that the BABRI Brain Health System had high stability.Conclusions:BABRI Brain Health System has not only high sensitivity and specificity, but also wide cognitive field coverage and high stability.BABRI Brain Health System is suitable for large-scale brain health examination and dementia risk screening in grass-roots communities, and is worthy of popularization.

Objective:To develop rapid screening tools for assessing the risk of mild cognitive impairment(MCI)based on neuropsychological scales and cognitive paradigms.Methods:Two baseline datasets from the Beijing Ageing Brain Rejuvenation Initiative(BABRI)cohort were studied: dataset 1 contained 5 593 subjects, with 1 500 cases with MCI and 4 093 cases with normal cognitive function(the control group); dataset 2 consisted of 588 subjects, with 92 cases with MCI and 496 cases with normal cognitive function(the control group). Dataset 1 was used to simplify the Mini-Mental State Examination(MMSE), and the sub-item combination with the strongest MCI discriminative ability was selected to integrate into the cognitive rapid assessment(BABRI-mini MMSE). Dataset 2 with scores of encoding-recognition episodic memory task was used for further MCI discriminant analysis and was adapted into an episodic memory test(BABRI-EMT). We applied the receiver operating characteristic curve(ROC)for those analyses.Results:The control group and the MCI group showed significant differences in multi-domain cognitive ability and episodic memory task performance( P<0.01). Among sub-items of MMSE measured using dataset 1, MMSE12 and MMSE19 had the highest discriminative accuracy for MCI, and the area under the ROC(AUC)was 0.699 and 0.631, respectively.Dataset 2 was used to investigate the discriminative ability of the episodic memory score in combination with the above two MMSE sub-items for MCI, and the AUC value was 0.732, the sensitivity was 0.731, and the specificity was 0.656. Conclusions:The BABRI-mini MMSE and BABRI-EMT are suitable for the large-scale universal screening of MCI risk.

Uridine-cytidine kinase, an important catalyst in the compensation pathway of nucleotide metabolism, can catalyze the phosphorylation reaction of cytidine to 5'-cytidine monophosphate (CMP), but the reaction needs NTP as the phosphate donor. To increase the production efficiency of CMP, uridine-cytidine kinase gene from Thermus thermophilus HB8 and polyphosphate kinase gene from Rhodobacter sphaeroides were cloned and expressed in Escherichia coli BL21(DE3). Uridine-cytidine kinase was used for the generation of CMP from cytidine and ATP, and polyphosphate kinase was used for the regeneration of ATP. Then, the D403 metal chelate resin was used to adsorb Ni²⁺ to form an immobilized carrier, and the immobilized carrier was specifically combined with the recombinant enzymes to form the immobilized enzymes. Finally, single-factor optimization experiment was carried out to determine the reaction conditions of the immobilized enzyme. At 30 °C and pH 8.0, 60 mmol/L cytidine and 0.5 mmol/L ATP were used as substrates to achieve 5 batches of high-efficiency continuous catalytic reaction, and the average molar yield of CMP reached 91.2%. The above method has the advantages of low reaction cost, high product yield and high enzyme utilization rate, and has good applied value for industrial production.
Cytidine Monophosphate ; metabolism ; Escherichia coli ; genetics ; Industrial Microbiology ; methods ; Phosphotransferases (Phosphate Group Acceptor) ; metabolism ; Uridine Kinase

BACKGROUND: Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells. METHODS: EA.hy926 cells, a kind of vascular endothelial cell, were used as the research model. The effects of PD 0332991 on the activity and proliferation of EA.hy926 cells were detected by the MTT, EdU assays. Wound-healing assays and transwell assays were used to determine the effects of PD 0332991 on the mobility of EA.hy926. The influence of PD 0332991 on cell cycle and apoptosis of endothelial cells was tested by flow cytometry, and the Western blot was applied to observe the expression of cell cycle related proteins in EA.hy926 cells treated by PD 0332991. RESULTS: PD 0332991 significantly inhibited the proliferation and mobility of EA.hy926 cells, caused cell cycle arrest and apoptosis. At the same time, PD 0332991 inhibited the expression of CDK4/6 and phosphorylation of Rb, and thus inhibited the cell cycle progression of EA.hy926 cells. CONCLUSIONS PD 0332991 can inhibit the proliferation and activity of endothelial cells and induces apoptosis.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 4 ; genetics ; metabolism ; Cyclin-Dependent Kinase 6 ; genetics ; metabolism ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Mice ; Piperazines ; pharmacology ; Pyridines ; pharmacology

Objective: To discuss the clinical results of three-stage functional ear reconstruction for microtia with congenital aural stenosis (CAS). Methods: From September 2007 to June 2017, 53 cases of microtia with CAS underwent all three-stage functional ear reconstruction, and 445 cases of microtia underwent two stage ear reconstruction without meatoplasty at the same periods. First-stage of three-stage functional ear reconstruction: it was similar to Nagata technique. The crus of helix could not be too long, since we needed the space for the next meatoplasty. Second-stage: it was a modified meatoplasty with endoaural-conchal incision, in which two local rotation flaps and a transposition split-thickness scalp flap were used to widen the stenotic external auditory canal (EAC) and reconstructed the tympanic membrane. Third-stage: it was a modified technique for firm elevation of the reconstructed auricle by using the retro-auricular fascial flap wrapping a porous polyethylene (Medpor) wedge or stored cartilage as the strut. If the patient showed EAC cholesteatoma or infection, we could do the meatoplasty at the first stage. If the patient had completed ear reconstruction, meatoplasty could be done at the third stage. Results: 53 cases underwent all three-stage functional ear reconstruction. There were 41 cases (77.4%) obtaining serviceable hearing. The complication rate of meatoplasty was 1.89% and the complication rate of ear reconstruction was 5.66%. Among the 445 cases of microtia treated with two stage ear reconstruction without meatoplasty, the complication rate of ear reconstruction was 9.43%. There was no significant difference between the two groups (P>0.05). Conclusions Our novel three-stage functional ear reconstruction is a feasible strategy for microtia with CAS. The patients can obtain satisfactory auricle and serviceable hearing. The results are stable and can improve the life quality in both aesthetics and hearing function.