Objective:To explore the microbiological and disease distribution characteristics of multidrug-resistant bacteria in patients hospitalized in a critical care rehabilitation ward, and to analyze the risk factors leading to multidrug-resistant bacterial infections.Methods:Microbiology screening data describing 679 patients admitted to a critical care rehabilitation ward were retrospectively analyzed to divide the subjects into a multidrug-resistant group (positive for multidrug-resistant bacterial infections, n=166) and a non-multidrug-resistant group (negative for multidrug-resistant bacterial infections, n=513). The risk factors were then analyzed using logistic regression. Results:Among 369 strains of multidrug-resistant bacteria observed, 329 were gram-negative bacteria (89.2%), mainly Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. They were distributed in sputum (56.9%) and mid-epidemic urine (28.2%) specimens. Patients whose primary disease was hemorrhagic or ischemic cerebrovascular disease accounted for 40.96% and 23.49% of the multidrug-resistant bacterial infections, respectively. Logistic regression analysis showed that albumin level, dependence on mechanical ventilation, central venous cannulation, or an indwelling urinary catheter or cystostomy tube were significant independent predictors of such infections.Conclusion:The multidrug-resistant bacterial infections of patients admitted to the critically ill rehabilitation unit are mainly caused by gram-negative bacteria. Their occurrence is closely related to low albumin levels and mechanical ventilation, as well as to bearing an indwelling central venous catheter, a urinary catheter or a cystostomy catheter.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To explore the effects and mechanisms of deoxycholic acid(DCA)on oxidative stress in human BAR-T cells.Methods The human Barrett epithelial cell line BAR-T was cultured in vitro,and the BAR-T cells were intervened with different concentrations of DCA(100,200,and 300 μmol/L)and different action time(30 min,60 min,3 h and 6 h).The mRNA and protein expression of COX-2 were detected by Real-time PCR and Western blotting assay.The intracellular reactive oxygen species(ROS)content was detected by direct microscope observation and flow cytometry,and was compared with that of 200 μmol/L DCA+5 mmol/L NAC(ROS scavenger N-acetylcysteine)group;cellular immunofluorescence was used to detect the entry of cellular p65 protein into the nucleus,which was then compared with 200 μmol/L DCA+PDTC(100 μmol/L,NF-κB pathway inhibitor)group.Results Compared to the control group,DCA increased ROS content in BAR-T cells in a dose-dependent manner.Additionally,5 mmol/L NAC significantly inhibited DCA-induced ROS release.Furthermore,both 200 μmol/L and 300 μmol/L DCA significantly increased COX-2 mRNA expression compared to the control group at the same intervention time.The 6 h groups for both 200 μmol/L and 300 μmol/L DCA showed a significant increase in COX-2 mRNA expression compared to the 1 h group.Compared to the control group,treatment with 200 μmol/L DCA significantly increased the expression of COX-2 protein.Meanwhile,200 μmol/L DCA promoted the nucleation of p65 protein,which was inhibited by PDTC.Conclusion DCA activates the NF-κB signaling pathway and upregulates the expression of COX-2 by elevating the intracellular ROS expression and promoting the entry of p65 protein into the nucleus.

Objective To explore the photodynamic treatment method and therapeutic effect of oral verrucous carci-noma and to provide a reference for the clinic.Methods This study follows the requirements of medical ethics.This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.Results After four rounds of photodynamic therapy,the size of the right buccal lesion was significantly reduced.After 6 months of follow-up,the white verrucous hyperplasia of the right buccal mucosa had completely subsided,and there was no obvious scar formation.Three years after treatment,there was no recurrence of the lesion in the right buccal mu-cosa and no obvious scar formation in the treated area.The degree of mouth opening was 3 fingers,and there was no lymph node enlargement in the bilateral submandibular,submental or neck.The literature review shows that oral verru-cous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth,low malignancy,and rare metastasis.Surgery is the preferred treatment,but there are some limitations.Photody-namic therapy is a minimally invasive,repeatable treatment with mild adverse reactions.In recent years,photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results,but it has not been reported for the treatment of oral verru-cous cancer.Conclusion Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Objective To evaluate the impact of ultra-high-molecular-weight polyethylene(UHMWPE)-Ribbond fi-bers,when combined with different restorative materials,on fracture resistance and marginal adaptation of isolated pri-mary molar defects,to provide a reference for clinical practice.Methods This study was approved by the Ethics Re-view Committee.A total of 72 extracted primary molars with complete crowns were collected,and 66 primary molars were randomly assigned as experimental groups for the fracture resistance and microleakage tests.The molars were di-vided into six groups(n=11)based on the type of restorative materials and the application of Ribbond fibers:Group A1,3M Filtek Z250+Ribbond;Group A2,3M Filtek Z250;Group B1,Beautifil Ⅱ LS+Ribbond;Group B2,Beautifil Ⅱ LS;Group C1,3M Filtek Bulk Fill+Ribbond;and Group C2,3M Filtek Bulk Fill.Groups A1,B1 and C1 received the fiber-reinforcing technique,whereas Groups A2,B2 and C2 received the direct restorative technique;the remainings were in Group D(blank control group),which did not receive treatment for the fracture resistance test.The fracture re-sistance test was divided into six experimental groups and one blank control group(n=6).Primary molar teeth in each experimental group were prepared with Class Ⅱ cavities and filled.The fracture load of all samples was detected,and the fracture mode was analyzed after thermal cycling.The microleakage test was divided into six experimental groups,with five in each group.Class Ⅰ cavities with a diameter of 3 mm and depth of 2.5 mm were prepared within the mesial and distal marginal ridges on the occlusal surface and filled for primary molars in each group.Marginal microleakage was assessed after thermal cycling.Results The fracture resistance test results showed that the fracture resistance in groups that received the fiber-reinforcing technique was greater than that in groups that received the direct restorative technique:Group A1>Group A2,Group B1>Group B2,Group C1>Group C2(P<0.05).The application of Ribbond fibers increased fracture resistance to all tested restorative materials by 37.08％to 39.34％.The proportion of tooth frac-ture decreased significantly in groups A1,C1 compared with A2,C2,with a significant increase in the occurrence rate of"Repairable"(P<0.05).The fracture resistance in Group A1 was significantly greater than that in Group B1 and Group C1(P<0.05).The marginal microleakage test results showed that the microleakage depth in groups that received the fiber-reinforcing technique was smaller than that in groups that received the direct restorative technique:Group A1

The second plenary session of the 20th Central Commission for Discipline Inspection proposed the"develop-ment of a five-year plan for information technology construction to establish a digital disciplinary inspection and supervision system that covers the entire process and all elements."This provides guidance and momentum for disciplinary inspection agencies at all levels to implement the strategic deployment of the Party's 20th National Congress regarding comprehensive and strict governance of the Party.In this context,utilizing information technology to enhance the efficiency of supervision,discipline enforcement,and accountability while ensuring the high-quality development of public hospitals has become a key task for their disciplinary inspec-tion departments.The Disciplinary Inspection Commission of a public hospital has explored the establishment of a disciplinary in-spection management platform to achieve modular management of inspection tasks.By utilizing functions such as task allocation,statistical analysis,data migration,and early warning reminders,the platform aims to improve the efficiency of disciplinary in-spection work.This approach helps address the challenges of heavy workloads and limited inspection resources in hospitals,enab-ling real-time supervision,early warning correction,and time-bound oversight,thereby providing strong support for the construc-tion of integrity in the hospital.

Objective To address the challenges of poor performance and lack of interpretability in existing models,the SHAP algorithm is used to develop an interpretable machine learning model that offers a novel approach to wound age estimation,Methods Based on the previous discovery of the expression of 35 wound age healing-related genes in contused skeletal muscle,the woun age estimaton model was constructed using four algorithms,namly,Multilayer Perceptron(MLP),Random Forest(RF),LightGBM(LGBM),and Support Vector Machine(SVM).The SHAP(Shapley Additive Explanation)algorithm was used to rank the importance of genetic features,eliminate redundant attributes,and optimize the model for accurate wound age estimation.the genetic features of the optimal model were analyzed using SHAP's local interpretation capabilities.Results The best results were obtained using model of MLP(area under the curve(AUC)=0.99)The wound ages were classified into four categories:4～12 h,16～24 h,28～36 h,and 40～48 h,using only 15 gene features.According to SHAP analysis,Fam210a was identified as the most relevant gene.Local analysis revealed that high expression of Fam210a contributed to an increase in the predicted probability of 4 h～12 h,while high expression of Rae1 contributed to an increase in the predicted probability of 16 h～24 h.Additionally,low expression of Tbx18 contributed to an increase in the predicted probability of 28 h～36 h,whereas high expression of Tbx18 contributed to an increase in the predicted probability of 40 h～48 h.Conclusions The combined MLP and SHAP model can be used to predict wound age.Using the SHAP interpreter can better understand the degree of contribution of feature genes to the model prediction,and lay the foundation for further in-depth study of wound age estimation.

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
Humans ; Gene Expression Profiling ; Neoplasms/genetics* ; Organ Specificity ; RNA, Long Noncoding/genetics* ; Transcriptome

Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.