Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.

Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.

Objective:To investigate the pathogenesis and clinical manifestations of anaphylactic shock and to evaluate the effectiveness of existing treatments, so as to improve the understanding of anaphylactic shock and to properly manage patients with anaphylactic shock.Methods:A retrospective observational study was conducted to select 63 patients with anaphylactic shock who were diagnosed and treated in Peking University First Hospital from July 2017 to June 2023 as the study objects, and the clinical data including basic information, present medical history, vital signs, past medical history, emergency treatment measures and prognosis were collected, and the causes, clinical manifestations and emergency treatment measures of anaphylactic shock were descriptively analyzed.Results:The causes of anaphylactic shock in 63 subjects could be divided into drug allergy (50.79%), food allergy (15.87%), blood product allergy (11.11%), others (3.17%), radiotherapy (1.59%), strenuous exercise (1.59%), hemodialysis (1.59%), and the triggers in 9 cases (14.29%) were unclear. The clinical manifestations can be abnormalities of the skin, respiratory system, cardiovascular system, gastrointestinal system and urinary system, among which the most common skin manifestations are wheal rash, itching, redness and swelling (79.37%), the most common manifestation of the respiratory system is dyspnea (30.16%), and the highest proportion of cardiovascular manifestations is blood pressure lower than 90 mmHg or baseline blood pressure drop of 30 mmHg (100.00%). The most commonly used therapeutic drugs were epinephrine (49.2%), glucocorticoids (69.8%), antihistamines (52.4%), vasopressors (12.7%), and others.Conclusion:The causes of anaphylactic shock are different, and the clinical manifestations are complex and diverse, and the condition can be severe and life-threatening. Clinically, attention should be paid to the early and accurate identification of high-risk patients, the prevention of anaphylactic shock, and the timely taking of corresponding measures to protect the life safety of patients once anaphylactic shock occurs. Early diagnosis and prompt treatment are key to managing anaphylactic shock.

The neuroimmune mechanism of rosacea has not been fully elucidated, and it is believed that the innate immune system, immune cells, immune regulation, neuroimmune system, signaling pathway abnormalities and microbial dysbiosis are involved in the progress of the neuroimmune mechanism of rosacea. This article reviews the neuroimmune mechanism of rosacea.

Objective:To investigate the pathogenesis and clinical manifestations of anaphylactic shock and to evaluate the effectiveness of existing treatments, so as to improve the understanding of anaphylactic shock and to properly manage patients with anaphylactic shock.Methods:A retrospective observational study was conducted to select 63 patients with anaphylactic shock who were diagnosed and treated in Peking University First Hospital from July 2017 to June 2023 as the study objects, and the clinical data including basic information, present medical history, vital signs, past medical history, emergency treatment measures and prognosis were collected, and the causes, clinical manifestations and emergency treatment measures of anaphylactic shock were descriptively analyzed.Results:The causes of anaphylactic shock in 63 subjects could be divided into drug allergy (50.79%), food allergy (15.87%), blood product allergy (11.11%), others (3.17%), radiotherapy (1.59%), strenuous exercise (1.59%), hemodialysis (1.59%), and the triggers in 9 cases (14.29%) were unclear. The clinical manifestations can be abnormalities of the skin, respiratory system, cardiovascular system, gastrointestinal system and urinary system, among which the most common skin manifestations are wheal rash, itching, redness and swelling (79.37%), the most common manifestation of the respiratory system is dyspnea (30.16%), and the highest proportion of cardiovascular manifestations is blood pressure lower than 90 mmHg or baseline blood pressure drop of 30 mmHg (100.00%). The most commonly used therapeutic drugs were epinephrine (49.2%), glucocorticoids (69.8%), antihistamines (52.4%), vasopressors (12.7%), and others.Conclusion:The causes of anaphylactic shock are different, and the clinical manifestations are complex and diverse, and the condition can be severe and life-threatening. Clinically, attention should be paid to the early and accurate identification of high-risk patients, the prevention of anaphylactic shock, and the timely taking of corresponding measures to protect the life safety of patients once anaphylactic shock occurs. Early diagnosis and prompt treatment are key to managing anaphylactic shock.

The neuroimmune mechanism of rosacea has not been fully elucidated, and it is believed that the innate immune system, immune cells, immune regulation, neuroimmune system, signaling pathway abnormalities and microbial dysbiosis are involved in the progress of the neuroimmune mechanism of rosacea. This article reviews the neuroimmune mechanism of rosacea.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

【Objective】 To investigate the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (M-TESE) in patients with non-obstructive azoospermia (NOA) caused by different causes. 【Methods】 A retrospective analysis was performed on 225 NOA patients during Jan.2020 and Dec.2022. The relation between SRR and patients’ age,body mass index (BMI),testicular volume,endocrine hormones and different etiological classifications were analyzed. 【Results】 According to whether sperm was obtained by surgery,the patients were divided into two groups,including 107 cases in the sperm group and 118 cases in the non-sperm group. There were no significant differences in patients’ age,testicular volume and levels of endocrine hormones between the two groups (P>0.05). According to the different causes,NOA patients with mumps history,cryptorchidism history,AZFc deletion or Klinefelter syndrome (KS) had higher SRR,while idiopathic NOA patients had the lowest SRR (P<0.05). 【Conclusion】 M-TESE is an effective treatment of NOA. There is no correlation between SRR and patients’ age,MBI,testicular volume and levels of endocrine hormones. NOA caused by different etiological classifications may have different SRR.

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.