ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

Objective:To explore the current situation and influencing factors of amputation decision-making dilemma of diabetic foot patients.Methods:From July to December 2023, 200 patients with diabetic foot in the Tianjin Medical University General Hospital and Tianjin Medical University Chu Hsien-I Memorial Hospital were selected as study subjects by convenience sampling. General Information Questionnaire, Decisional Conflict Scale (DCS), Family APGAR Index, and Hospital Anxiety and Depression Scale were used to conduct a cross-sectional survey. Pearson correlation was used to analyze the correlation between diabetic foot patients' amputation decision-making dilemma and family caring, anxiety and depression, and multiple linear regression was used to analyze the influencing factors of diabetic foot patients' amputation decision-making dilemma.Results:A total of 200 questionnaires were distributed, and 180 valid questionnaires were collected, with a valid response rate of 90.0% (180/200). The DCS score of 180 patients with diabetic foot was (30.04±9.77), 76.7% (138/180) patients scored ≥25.0, and they had decision-making dilemma, and 25.0% (45/180) of patients scored ≥37.5, indicating decision-making delay. Multiple linear regression analysis showed that occupational status, diabetes course, family caring, anxiety and depression were the influencing factors of amputation decision-making dilemma of diabetic foot patients ( P<0.05) . Conclusions:Diabetic foot patients face certain dilemmas in the process of amputation decision-making. Clinical medical and nursing staff should reasonably evaluate the patient's occupational status, disease course, family caring, and psychological state, and develop personalized decision support strategies to improve decision quality and prevent changes in the patient's condition caused by delayed decision-making.

In order to detect the environmental data of isolated cabin under various environmental conditions,a negative pressure cabin environment detector for aviation was developed,which was composed of a shell,a differential pressure transmitter,a pressure sensor,a carbon dioxide concentration sensor,an oxygen concentration sensor,a temperature and humidity sensor,a data processing module,a liquid crystal display(LCD)screen and USB data interface.It could environmental data such as carbon dioxide concentration,oxygen concentration,temperature,humidity,pressure difference between cabin and outside the cabin and air pressure outside the cabin in real time,the data processing module collected and processed the data,the data and data change curves was displayed in real time by the LCD screen,and the detection data was extracted through the USB data interface.When used in aviation environment,the detector could work continuously without fault for no less than 300 hours,and the average fault repair time was about 30 minutes,with good performance and high detection accuracy,which can provide convenience for the environmental data detection of negative pressure cabins,and is worthy of popularization.

Globally, gynecological malignancies are common types of female cancer and the main cause of cancer death among women. Cervical cancer, endometrial cancer and ovarian cancer, which are the main types of gynecological cancers, pose a significant threat to women's health worldwide. Studies have shown that diet plays an important role in the occurrence and development of gynecological cancers such as cervical cancer, endometrial cancer, and ovarian cancer, for which added sugar may be an influencing factor due to its food source characteristic and related biological effect. However, this paper reviewed the research progress on the relationship between consumption of added sugar and gynecological cancers such as endometrial cancer, ovarian cancer and cervical cancer, with a view to providing a reference for the active prevention of gynecological cancer.

Objective:To study the specific mechanism of LINC01018 involved in the pathogenesis of colon cancer.Methods:The expression of LINC01018 in colon cancer tissues and cells and normal colon tissues and cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cell line which overexpresses LINC01018 stably was established. RNA binding protein immunoprecipitation (RIP) assay was used to detect the interaction between LINC01018 and E2F1 protein. Dual luciferase assay was used to detect the regulatory effect of E2F1 on CDK6 promoter. The expression of E2F1 or CDK6 was up-regulated in HT-29 cell line which overexpresses LINC01018, then the proliferation, invasion and migration of HT-29 cells and the expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells were detected by cell counting method (CCK-8) assay, Transwell assay and Western blot.Results:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. The result of RIP assay showed that LINC01018 interacted with E2F1 protein. The result of dual luciferase assay showed that E2F1 protein could enhance the efficiency of CDK6 promoter, and E2F1 had a positive regulatory effect on CDK6. Overexpression of LINC01018 could attenuate the positive regulatory effect of E2F1 on CDK6. Up-regulation of E2F1 or CDK6 expression could attenuate the effects of LINC01018 overexpression on the proliferation, invasion, migration and expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. LINC01018 may regulate the proliferation, invasion and migration of HT-29 cells through E2F1/CDK6/MMP-2 axis, and participate in the pathogenesis of colon cancer.

Objective To investigate the distribution and drug resistance of carbapenem-resistant Enterobacteriaceae ( CRE) isolated from children in China. Methods CRE strains were collected in 10 ter-tiary children's hospitals of China from January 1, 2016 to December 31, 2017. Antimicrobial susceptibility of the clinical strains was detected with disk diffusion method ( KB method) and automated method. The re-sults were analyzed according to the Clinical and Laboratory Standards Institute ( CLSI) Standards published in 2017. WHONET 5. 6 software was used to retrospectively analyze the distribution characteristics and drug resistance of these strains. Results A total of 3065 CRE clinical strains were isolated from children with an overall prevalence of 7. 7％ and among them, 13. 5％ were isolated in neonatal group and 5. 8％ in non-neo-natal group. The detection rate of CRE in 2017 was higher than that in 2016 (9. 7％ vs 5. 7％). Among the 3065 CRE strains, there were 1912 strains of Klebsiella pneumoniae (62. 0％), 667 strains of Escherichia coli (22. 0％), 206 strains of Enterobacter cloacae (7. 0％), 56 strains of Klebsiella aerogenes (1. 8％) and 47 strains of Serratia marcescens (1. 5％). Most of the strains were isolate in neonatology departments including neonatal intensive care units (NICU) and intensive care units (ICU), accounting for 44. 8％ and 19. 7％, respectively. Respiratory tract (61. 8％), urine (19. 4％) and blood (5. 7％) specimens were the main sources of CRE isolates. Results of antimicrobial susceptibility test showed that the CRE strains were highly resistant to carbapenem antibiotics such as imipenem, meropenem and ertapenem, as well as penicillins and most cephalosporins (79. 6％-100％), especially those isolated in the neonatal group (P<0. 05). Children had relatively low resistance rates to aminoglycosides such as amikacin (19. 7％) and fos-fomycin (11. 9％), fluoroquinolones such as levofloxacin (37. 7％) and ciprofloxacin (43. 3％), and tige-cycline (3. 8％). Currently, no polymyxin B-resistant strains were isolated. Conclusions The prevalence of common CRE strains in children in 2017 was higher than that in 2016, especially in newborns. Drug re-sistance in CRE strains isolated from neonates to common antibiotics was more severe, suggesting that great attention should be paid to it and timely measures should also be taken.

Objective To investigate the mechanism of efflux pump AcrAB-TolC involved in the cross-resistance between quaternary ammonium compounds ( QAC) and fluoroquinolones ( FQ) in Escherich-ia coli. Methods Seventy-eight Escherichia coli strains were isolated from clinical samples and then tested for the sensitivity to benzalkonium bromide by ager dilution method. Six strains were randomly selected and induced with benzalkonium bromide. Changes in the sensitivity of these strains to benzalkonium bromide and ciprofloxacin were analyzed after induction. Expression of the efflux pump genes acrA, acrB and tolC at mRNA level in the induced strains and their parent strains were detected by quantitative real-time PCR. Re-sults Among the 78 strains, the minimum inhibitory concentrations ( MIC) ranged from 8 μg/ml to 64μg/ml and 47. 4％ of strains have higher MIC than the standard strain. Compared with the parent strains, the induced strains showed higher expression of acrA and tolC genes, and the differences between the two groups were statistically significant. The MIC values of ciprofloxacin to the six induced strains were 4-8 times higher than those to their parent strains. Conclusions It was speculated that the increased expression of acrA and tolC genes at transcription level in the induced strains were related to the cross-resistance between quaternary ammonium compounds and fluoroquinolone antibiotics.

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.
Animals ; Aurora Kinase B ; metabolism ; Aurora Kinase C ; metabolism ; Blastocyst ; metabolism ; Gene Expression Regulation, Developmental ; physiology ; Histones ; metabolism ; Mice ; Phosphorylation ; physiology

A 26?year?old male patient presented with facial depigmented patches for 10 years, some of which turned to blue?grey 7 years prior to the presentation. Before the white patches turned blue?gray, the patient developed contact dermatitis due to topical application of self?made drugs. Skin examination showed blue?gray hyperpigmentation on the left upper lip and in the temporal region, with white hairs in the hyperpigmented lesions on the left upper lip. Dermoscopy revealed irregularly shaped, light to dark blue?gray patches on the left upper lip, which were intermingled with white patches in some regions, and white hair stubs were observed in the white patches. Histopathological examination of temporal lesions showed decreased melanocytes in some regions in the epidermis, pigmentation in both basal and suprabasal layers, perivascular infiltration of a small number of chronic inflammatory cells and melanophages in the superficial dermis, and melanophage infiltration around sweat ducts. Finally, the patient was diagnosed with blue vitiligo. He refused to receive any treatments, and follow?up was under way.

A sequential clean-up method was developed for the quantification of 10 plant growth regulators in bean sprout by the gas chromatography / mass spectrometry (GC / MS). The analytes were firstly extracted by the acided acetonitrile. Extraction was concentrated and re-dissovled by methanol. Then, it was divided to two aliquots. One of that was analyzed for 2,4-D-butyl ester and 2,4-D-ethyl ester after the purification by QuECHERS cartridge. Another one was treated by MCS solid phase extraction column including diverse eluting steps. After eluting by 5 mL methanol, composition 1 was obtain, concentrated, and methyl esterified by 10% boron trifluoride methanol solution. The treated extract was used for the determination of 4-chlorophenoxy acetic acid, β-naphthyl acetic acid, 2,4-dichlorophenoxy acetic acid, indole acetic acid and indole butyric acid. Composition 2 collected by eluting with 5 mL 5% amonium methanol was used for the determination of paclobutrazol, Kinetin, 6-Benzylaminopurine. The clean-up procedures are designed according to different chemistry properties of these plant growth regulators. The results showed that after spiking of 0. 01-0. 1 mg / kg selected plant growth regulators, average recovery ranged from 70. 0% to 93. 2%and relative standard deviation were 5. 2% -12. 3% . Limit of quantification (LOQ S / N≥10) and limit of detection (LOD S / N≥3) were 0. 01-0. 025 mg / kg and 0. 003-0. 008 mg / kg respectively. The developed purification method is easy, fast and accurate, and can be applied to routine test of plant growth regulators in bean sprout.