Objective The amplitude of low-frequency fluctuation(ALFF)resting state functional magnetic resonance imaging(rs-fMRI)was used to investigate the signals image in the brain functional areas of overactive bladder(OAB)patients.Methods OAB patients treated in 3 participating hospitals during Mar.2021 and Mar.2023 were selected as the OAB group(n=14).Healthy subjects matching the gender,age and years of education of the patients in the OAB group were collected as the control group(NC group,n=14).Changes in the over active bladder symptom score(OABSS),quality of life scale(QoL),self-rating depression scale(SDS),self-rating anxiety scale(SAS)were analyzed.All subjects underwent rs-fMRI to collect blood oxygen level dependent magnetic resonance signals,which were then processed with ALFF.Two-sample t-test was conducted on the results to obtain the different brain regions.Results The OABSS[(8.07±0.37)vs.(1.21±0.18)],QoL[(4.85±0.21)vs.(0.64±0.13)],SAS[(60.14±1.40)vs.(37.64±1.57)]and SDS[(52.50±1.29)vs.(36.14±0.34)]scores of the OAB group were higher than those of the NC group,with significant differences(P＜0.05).The brain regions with significant differences in ALFF were located in the left supplementary motor area,left medial superior frontal gyrus and right anterior central gyrus(P＜0.000 1).Conclusion The abnormal spontaneous activity and coordination ability of the brain in resting state may lead to OAB symptoms,which are displayed in the abnormal functions of the left supplementary motor area,left medial superior frontal gyrus and right anterior central gyrus.

Compared with simple stress urinary incontinence (SUI), complicated female SUI is more diverse in etiology and more difficult to treat.Based on domestic and foreign literature and our diagnosis and treatment experience, this paper makes a detailed introduction to the definition, diagnosis, evaluation and clinical treatment of complicated female SUI, so as to provide guidance and reference for the treatment of this disease.

Objective To explore the evaluation value of forkhead box M1(FOXM1)and CC chemokine receptor 5(CCR5)on lung function and prognosis in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 128 AECOPD patients admitted to Yueyang People's Hospital from January 2022 to January 2023 were collected as the acute exacerbation group,135 stable COPD patients admitted at the same time were regarded as the stable phase group,and 120 health examination volunteers of similar age and gender were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression levels of FOXM1 and CCR5 in serum,and the vital capacity meter was applied to measure pulmonary function.Pearson method was applied to analyze the correlation between serum FOXM1,CCR5 and lung function indicators in AECOPD patients.Multivariate logistic regression analysis was applied to screen prognostic factors for AECOPD patients.The evaluation value of FOXM1 and CCR5 levels in evaluating poor prognosis of AECOPD patients was analyzed by receiver operating characteristic(ROC)curve.Results In the serum of patients in the AE COPD group and stable stage group,the levels of CCR5(49.36±12.31 ng/ml,34.25±8.87 ng/ml)and FOXM1(40.21±10.74 pg/ml,23.38±5.77 pg/ml)were significantly higher than those in the control group(14.55±4.58 ng/ml,15.06±3.55 pg/ml),while FEV1(1.15±0.13 L,1.67±0.19 L),FVC(2.93±0.30 L,3.28±0.36 L)and FEV1/FVC(39.25％±3.97％,50.91％±5.01％)were lower than those in the control group(1.95±0.26 L,3.57±0.44 L,54.62％±5.20％),with significant differences(F=11 1.034～641.907,all P＜0.05).The levels of serum FOXM1 and CCR5 were gradually increased with the aggravation of lung function grading,while the levels of lung function indicators FEV1 and FVC were gradually decreased with the aggravation of lung function grading,and the differences were statistically significant(F=31.27,49.37;42.72,29.48,all P＜0.05).The serum levels of FOXM1 and CCR5 were negatively correlated with FEV1,FVC and FEV1/FVC(r=-0.639～-0.479,all P＜0.05).Logistic regression analysis found that CCR5[OR(95％CI):3.380(1.944～5.876)],FOXM1[OR(95％CI):5.711(3.175～10.273)],APACHE Ⅱ score[OR(95％CI):2.132(1.243～3.660)],and lung function grading[OR(95CI):2.017(1.007～4.037)]were all risk factors for poor prognosis(all P＜0.05),while FEV1[OR(95％CI):0.649(0.441～0.955)]and FVC[OR(95％CI):0.120(0.073～0.198)]were protective factors for poor prognosis(all P＜0.05).ROC curve results showed that the areas under the curve(AUC)of serum FOXM1 and CCR5 levels in predicting poor prognosis in AECOPD patients were 0.821 and 0.831,respectively.The AUC predicted by the combination of the two was 0.895,which was higher than that detected by a single indicator(Z=2.800,2.654,all P＜0.05).Conclusion FOXM1 and CCR5 were both high levels in the serum of AECOPD patients.Early detection of them can serve as serum markers for evaluating lung function and poor prognosis in AECOPD patients.

Objective:To investigate the effect and mechanism of the V-set and immunoglobulin domain-containing 4 ( VSIG4 ) gene mutation on the function of microglia in retinitis pigmentosa (RP). Methods:Localization of VSIG4 in the retina was detected by immunofluorescence.HMC3 cells (human microglial cells) were transfected with wild-type (Len-WT) VSIG4 gene, mutant type (Len-Mut) VSIG4 gene and empty vector virus (Len-Cont) and stimulated by the presence or absence of lipopolysaccharide (LPS), then divided into control group, LPS-Len-Mut group, LPS-Len-WT group, LPS-Len-Cont group, Len-Mut group, Len-WT group and Len-Cont group.The mRNA expression levels of the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by real-time fluorescence quantitative PCR.Protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4), nuclear transcription factor-κB (NF-κB) p65 subunit (P65), and phosphorylated P65 (PP65) were detected by Western blot.Cell phagocytic function was detected by phagocytosis assay.Cell migration ability was detected by cell scratch and transwell migration assay.LPS- stimulated HMC3 cells were co-cultured with 661W cells (mouse retinal photoreceptor cells), and the expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins of the cells were detected by Western blot.The number of apoptotic cells was determined by apoptosis assay. Results:VSIG4 was localized to microglia in mouse retina.The real-time fluorescence quantitative PCR results showed that compared with LPS-Len-WT group, the relative expression levels of IL-1β and TNF-α mRNA in HMC3 cells were significantly increased in LPS-Len-Mut group (both at P<0.05).The Western blot results showed that compared with LPS- Len-WT group, the protein expression levels of Nrf2, HO-1, and GPX4 in HMC3 cells were significantly reduced in LPS-Len-Mut group, and the PP65/P65 ratio was significantly increased (all at P<0.05).The phagocytic experiment results showed that the phagocytic rates of HMC3 cells in Len-Cont group, LPS-Len-Cont group, LPS-Len-WT group, and LPS-Len-Mut group were (35.67±3.22)%, (63.67±10.07)%, (84.00±3.46)%, and (64.67±2.31)%, respectively, showing a statistically significant difference ( F=59.06, P<0.001).Compared with LPS-Len-WT group, the phagocytic rate of HMC3 cells was significantly reduced in LPS-Len-Mut group ( P<0.05).The results of cell scratch and transwell migration assay showed that compared with LPS-Len-WT group, the migration rate of HMC3 cells at 24 and 48 hours and the number of invading cells per unit area at 24 hours were significantly reduced in LPS-Len-Mut group (all at P<0.05).Compared with LPS-Len-WT group, the expression ratio of Bax/Bcl-2 protein and the number of cell apoptosis were significantly increased in the LPS-Len-Mut group under the co-culture system (both at P<0.05). Conclusions:VSIG4 is localized to mouse retinal microglia.When the VSIG4 gene in RP mutates, HMC3 cells under LPS stimulation exhibit a series of changes, including activation of the NF-κB signaling pathway, decreased activation of the Nrf2/HO-1 signaling pathway, increased secretion of inflammatory cytokines, reduced phagocytic and migratory abilities, and increased cell apoptosis in co-culture systems.

ObjectiveTo analyze the effects of polydatin on myeloma cell growth，apoptosis， and reactive oxygen species（ROS）/p38 mitogen-activated protein kinase（MAPK） signaling pathway. MethodHuman multiple myeloma （MM） cell line U266 cells were cultured in vitro，and the effects of polydatin at 0，20，40，80，160，200 mg·L^-1 on the growth of U266 cells were detected by cell counting kit-8（CCK-8）assay. The half-maximal inhibitory concentration（IC₅₀）was calculated. U266 cells in the logarithmic growth phase were randomly divided into a control group， low- and high-dose polydatin （80 and 160 mg·L^-1） groups， and a bortezomib （75 nmol·L^-1） group. After treatment with corresponding drugs，the cell viability of each group was determined by CCK-8 assay. The apoptosis rate of each group was measured by flow cytometry. The levels of inflammatory factors， such as tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）， and ROS in each group were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of apoptosis-related factors， including cysteine aspartate-specific protease-9（Caspase-9），B-cell lymphoma-2-associated X protein（Bax），p38 MAPK，and phosphorylated （p）-p38 MAPK in each group were detected by Western blot. ResultCompared with the results in the control group， polydatin of different concentrations could inhibit the growth of U266 cells （P<0.05），and the effect was potentiated with the increase in the concentration，with IC₅₀ of 156.54 mg·L^-1. Compared with the control group，the groups with drug treatment showed blunted cell viability （P<0.05） and increased apoptosis rate，TNF-α，IL-1β，and ROS levels， protein expression levels of Caspase-9， Bax，and p-p38 MAPK/p38 MAPK （P<0.05）. Compared with the low-dose polydatin group， the high-dose polydatin group and the bortezomib group showed improved indicators mentioned above （P<0.05）， and there was no significant difference between the high-dose polydatin group and the bortezomib group. ConclusionPolydatin can activate the ROS/p38 MAPK signaling pathway，promote the expression of inflammatory factors，inhibit the growth of U266 cells，and promote their apoptosis.

ObjectiveTo study the association of serum adiponectin and high sensitivity C-reactive protein (hs-CRP) levels to short-term outcome in patients with acute ischemic stroke (AIS). MethodsClinical data of 216 patients with AIS in Beijing Bo'ai Hospital from January, 2019 to September, 2020 were collected. The serum biochemical indicator was measured in all the patients within 24 hours after enrollment, and adiponectin was detected with enzyme-linked immunosorbent assay. Meanwhile, all patients were evaluated with National Institute of Health Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was used to assess the functional outcome 90 days after onset during follow-up. ResultsThe incidence of poor outcome in patients with AIS within 90 days was 48.1%. Compared with the good outcome group, the serum adiponectin was lower (t = 5.861, P < 0.001) and the serum hs-CRP level was higher (Z = 5.525, P < 0.001) poor outcome group. Reduced serum adiponectin (OR = 0.862, 95%CI 0.751 to 0.975, P < 0.001) and increased serum hs-CRP (OR = 1.215, 95%CI 1.015 to 1.455, P < 0.001) were independent risk factors for poor outcome in patients with AIS. The areas under curve (95% CI) of serum adiponectin and hs-CRP for predicting the outcome of patients with AIS were 0.819 (0.761 to 0.877) and 0.722 (0.654 to 0.791), respectively (P < 0.001). The predictive power of serum adiponectin was higher than that of hs-CRP (Z = 2.151, P = 0.032). The optimum cut-off point of adiponectin was < 3.5 mg/L, and the Yoden index was 0.609, yielding a sensitivity of 0.704 and a specificity of 0.905. ConclusionSerum adiponectin and hs-CRP can serve as independent predictors for short functional outcome in patients with AIS.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective To investigate the effects of the rhein on the mitochondria fission and epithelial-mesenchymal transition(EMT)of breast cancer cells MDA-MB-231.Methods Human breast cancer cells were intervened with rhein,and the cells were divided into control group(0 μmol·L-1),low dose rhein group(100 μmol·L-1),and high dose rhein group(200 μmol·L-1).The proliferation activity of the cells was detected by CCK-8,and migrations was detected by Scratch-healing migration assay.The morphology and distribution of mitochondria were detected by transmission electron microscope,and the expression levels of Dynamin-related protein 1(Drp1),mitofusin2(Mfn2),E-cadherin,Vimentin proteins were detected by Western blot.Results Compared with control group,Rhein significantly reduced the protein expression of Drp1、Vimentin(P<0.05),and increased E-cadherin and Mfn2,thus down-regulating mitochondria fission,inhibiting cell proliferation and migration.High dose Rhein was better than low dose.Conclusion Rhein can inhibit the proliferation and migration of breast cancer cells by reducing the expression of Drp1,Vimentin and up-regulating Mfn2,E-cadherin proteins.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Bioengineering majors require students to acquire excellent abilities of thinking and analyzing complex problems and have high requirements for students' comprehensive practical skills. Because of the professional characteristics, it is necessary to develop students' abilities to solve complex problems via the teaching of a series of experiments. Therefore, it is particularly important to reform the traditional experiment teaching for students majoring in bioengineering to improve the teaching quality, which have great significance for the cultivation of comprehensive talents. In this study, with the advantages of geographical location and resources to cultivate application-oriented innovative talents, the course group of Comprehensive Experiment of Bioengineering has designed the course based on virtual simulation technology in Binzhou University. Taking the experiment of extraction and bioactivity analysis of Suaeda salsa (growing in the Yellow River Delta) polysaccharide in fermentation as a case, we studied the course design idea, experimental process, teaching method and result analysis, and have improved the teaching performance. This case analysis provides new ideas and content reference for the teaching reform of similar courses.
Bioengineering/education* ; Biomedical Engineering/education* ; Humans ; Students ; Technology ; Universities