Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To develop nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia,and test its reliability and validity.Methods Based on the evidence-based summary of the best evidence of medication management for patients with dysphagia,guided by the the-ory of knowledge,attitude and practice,the basic dimensions and item pool of the questionnaire were deter-mined through group discussion,Delphi expert consultation and pre-investigation.In order to revise the ques-tionnaire,437 nurses from 10 tertiary hospitals in Jiangsu Province were conveniently selected for investigation,and the reliability and validity of the questionnaire were tested according to the survey results.Results The nurses'knowl-edge,attitude and practice questionnaire on medication management for patients with dysphagia included 43 items in three dimensions.The three dimensions were analyzed by exploratory factors,and six common factors with characteristic roots>1 were extracted.Two factors were extracted from the knowledge dimension,and the cumulative variance contribution rate was 74.958%,One factor was extracted from the attitude dimen-sion,and the cumulative variance contribution rate was 77.655%.Three factors were extracted from the prac-tice dimension,and the cumulative variance contribution rate was 72.274%.The factor load of each item was 0.618-0.902,Cronbach's α coefficient of the total questionnaire was 0.949,and the test-retest reliability was 0.909.The overall content validity coefficient of the questionnaire was 0.922,and the content validity coeffi-cient for each item was 0.800-1.000.Conclusion The nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia developed in this study has good reliability and validi-ty,and could be used as an effective tool to evaluate the status quo of nurses'medication management for pa-tients with dysphagia.

Objective To explore the mechanism of immediate effect regulated by acupuncture on acupoints in patients with migraine without aura(MwoA)during the interictal period.Methods A total of 28 MwoA patients were enrolled and resting-state functional magnetic resonance imaging(rs-fMRI)were performed at baseline and after acupuncture for 30 minutes.Paired t test was used to compare the differences of regional homogeneity(ReHo)and voxel-mirrored homotopic connectivity(VMHC)between two groups.Additionally,the correlation between the changes of rs-fMRI indexes and clinical scores was analyzed.Results In MwoA patients after acupuncture for 30 minutes,the mean regional homogeneity(mReHo)was decreased in the right lingual gyrus and right cere-bellum and was increased in the right middle frontal gyrus,while the z transformation voxel-mirrored homotopic connectivity(zVMHC)was significantly decreased in the bilateral cuneus compared with baseline.There was no significant correlation between imaging data and clinical scales.Conclusion Patients with MwoA after acupuncture for 30 minutes show abnormal ReHo and VMHC in multiple brain regions,which suggest that the mechanism of immediate effect may act through regulating pain-related brain regions.

Objective:To analyze the correlation between the skin temperature changes in the radiation area and the occurrence of radiodermatitis during postoperative radiotherapy for female breast cancer and to explore the application value of skin temperature monitoring in the early warning of radiodermatitis risks.Methods:A total of 103 patients who received three-dimensional conformal radiotherapy after radical mastectomy in the Fourth Hospital of Hebei Medical University were continuously enrolled from May to November, 2022 in this study. Their skin temperature in the radiation area and radiodermatitis were recorded weekly. The relationships between relative skin temperature differences and different grades of radiodermatitis were determined. The optimal cut-off values for grade ≥ radiodermatitis were calculated, and the predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Furthermore, the radiodermatitis risks under different skin temperatures were compared using binary logistic regression.Results:There was a positive correlation between the skin temperature in the radiation field and the grade of radiodermatitis. The optimal cut-off values for the average relative skin temperature difference of the chest wall (under 40 Gy/20 fractions), the maximum relative skin temperature difference of the chest wall (under 40 Gy/20 fractions), and the relative skin temperature difference of the supraclavicular block (under 30 Gy/15 fractions) were 0.45℃, 0.55℃, 0.15℃, respectively. The patients were divided into low- and high-risk groups based on the optimal cut-off values (0.45℃, 0.55℃, and 0.15℃). Binary logistic regression result showed that the risks of grade ≥ 2 radiodermatitis in the high-risk group were 5.71, 4.29, and 5.15 times those in the low-risk group, respectively ( OR = 5.71, 95% CI 1.81-17.99, P = 0.003; OR = 4.29, 95% CI 1.65-11.12, P = 0.003; OR = 5.15, 95% CI 2.16-12.31, P < 0.001). Conclusions:Skin temperature monitoring using medical infrared thermometers can be used to effectively predict the occurrence of grade ≥ 2 radiodermatitis. The skin temperature changes in the radiotherapy area should be closely observed. The risk of grade ≥ 2 radiodermatitis will increase when the mean and maximum relative temperature differences of the chest wall increase by 0.45℃ and 0.55℃, respectively under 40 Gy/20 fractions of radiotherapy or when the relative temperature differences of the supraclavicular block increases by 0.15℃ under 30 Gy/15 fractions of radiotherapy.

Pancreatic fibrosis (PF) is primarily distinguished by the stimulation of pancreatic stellate cells (PSCs) and excessive extracellular matrix deposition, which is the main barrier impeding drug delivery and distribution. Recently, nanomedicine, with efficient, targeted, and controllable drug release characteristics, has demonstrated enormous advantages in the regression of pancreas fibrotic diseases. Notably, paracrine signals from parenchymal and immune cells such as pancreatic acinar cells, islet cells, pancreatic cancer cells, and immune cells can directly or indirectly modulate PSC differentiation and activation. The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis. However, the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed. Herein, we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes. Then, we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis, thereby offering innovative insights for the design of antifibrotic nanomedicine. Ultimately, the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.

Objective:To explore the application value of 3D-slicer software in measuring renal volume parameters of renal transplant donors in evaluating renal function.Methods:The data of 31 renal donors admitted to Beijing Friendship Hospital, Capital Medical University from October 2019 to September 2022 were retrospectively analyzed. Glomerular filtration rate (GFR) were measured by SPECT radioactive dynamic imaging, and renal cortex volume (RCV), renal parenchymal volume (RPV) were measured after 3D reconstruction of urinary enhanced CT based on 3D slicer software. The estimated GFR(eGFR) predicted by creatinine-based GFR estimation equations (C-G equation, modified and simplified MDRD equation) and volume-based GFR estimation equations (Herts equation, Choi equation). Different eGFR were calculated, and the correlation between kidney volume parameters, eGFR equations and measured GFR was analyzed. The deviation, accuracy and consistency between different equations eGFR and measured GFR were analyzed and compared. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with non-normal distribution were represented by M( Q1, Q3), and non-parametric test was used for comparison between groups. Results:The correlation between different eGFR and measured GFR is poor, and the deviation is small, and with good accuracy and consistency. Except for the weak correlation between the Choi equation eGFR and measured GFR ( r=0.382, P=0.034), there was no significant correlation between eGFR by other equations and measured GFR ( P>0.05). Among them, the deviation between the Herts equation-eGFR and measured GFR was the smallest (0.30 mL·min -1·1.73 m -2), with a 10% coincidence rate (61.29%) and a 30% coincidence rate (96.77%), and the best consistency with measured GFR, with a consistency limit of -28.75 to 29.34 mL·min -1·1.73 m -2. Conclusion:Compared with the laboratory index formula method, the Herts equation has better prediction efficiency in estimating GFR, The measurement of renal volume parameters by 3D slicer software has a certain clinical value in evaluating the renal function of renal donors, which is worthy of further application.

Objective:To investigate the clinical characteristics and gene sequencing results of NDM, so as to provide evidence for clinical diagnosis and treatment .Methods:Clinical data of 1 child diagnosed with NDM in Hebei People's Hospital in January 2021 were retrospectively analyzed, and DNA gene sequencing was performed in the peripheral blood of the child, and relevant literatures were reviewed.Results:The child was born with a weight of 2.2kg. On the second day after birth, blood glucose significantly increased and insulin and C-peptide levels decreased. After 14 days of insulin treatment, hyperglycemia was still present, which was consistent with the diagnosis of NDM. Genetic testing indicated that there were missense mutations of newborn compound heterozygote in ABCC8 gene: c. 752G > A (p.G251E), c. 772A > G (p.R258G). The mutation of c. 772A > G in ABCC8 gene had not been reported before, and sulfonylureas were effective for the treatment of the child.Conclusion:NDM is a rare monogenic genetic disease with a lack of specificity in clinical manifestations. For children diagnosed or suspected of NDM, genetic testing should be actively carried out, which is of great significance for clinical diagnosis, treatment and prognosis.

Transcranial direct current stimulation (tDCS) has become a new method of post-stroke rehabilitation treatment and is gradually accepted by people. However, the neurophysiological mechanism of tDCS in the treatment of stroke still needs further study. In this study, we recruited 30 stroke patients with damage to the left side of the brain and randomly divided them into a real tDCS group (15 cases) and a sham tDCS group (15 cases). The resting EEG signals of the two groups of subjects before and after stimulation were collected, then the difference of power spectral density was analyzed and compared in the band of delta, theta, alpha and beta, and the delta/alpha power ratio (DAR) was calculated. The results showed that after real tDCS, delta band energy decreased significantly in the left temporal lobes, and the difference was statistically significant ( P < 0.05); alpha band energy enhanced significantly in the occipital lobes, and the difference was statistically significant ( P < 0.05); the difference of theta and beta band energy was not statistically significant in the whole brain region ( P > 0.05). Furthermore, the difference of delta, theta, alpha and beta band energy was not statistically significant after sham tDCS ( P > 0.05). On the other hand, the DAR value of stroke patients decreased significantly after real tDCS, and the difference was statistically significant ( P < 0.05), and there was no significant difference in sham tDCS ( P > 0.05). This study reveals to a certain extent the neurophysiological mechanism of tDCS in the treatment of stroke.
Brain/physiopathology* ; Brain Waves/physiology* ; Electroencephalography/methods* ; Humans ; Stroke/therapy* ; Stroke Rehabilitation/methods* ; Transcranial Direct Current Stimulation/methods*