It is very limited that the benefit of perioperative chemotherapy in early non-small cell lung cancer (NSCLC), and the 5-year survival rate is only 5% higher than surgery. Antibodies that block programmed cell death protein 1/programmed death-ligand 1 significantly improve the survival of advanced NSCLC. The value of immunotherapy in early NSCLC is also being explored. This paper firstly summarized and analyzed the progress of immunotherapy in the perioperative period of NSCLC. Secondly, the safety and feasibility of surgical resection after neoadjuvant immunotherapy were discussed. Finally, the clinical value of different therapeutic efficacy prediction indicators was summarized, in order to clarify the current status of immunotherapy in the perioperative period, so as to improve the clinical benefits of early NSCLC patients.

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis （NASH） at the single-cell level using single-cell RNA sequencing （scRNA-seq）， and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient （MCD） diet， with three mice in each group， and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets， and related analyses were performed， including dimension clustering， cell type annotation， t-distributed stochastic neighbor embedding （t-SNE）， violin plot， gene ontology （GO） functional enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice， and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2， Cd8b1， Cd8a， and Tcf7. Tcf7， a characteristic marker gene for cluster 6， was expressed in 65% of cells in cluster 6， and therefore， cluster 6 was defined as Tcf7⁺ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation， leukocyte adhesion， binding ubiquitin-like protein ligase， and the signaling pathways for Th17， Th1， and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg， Tcrg-C1， Il2rα， and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7， and therefore， cluster 7 was defined as Cxcr6⁺ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation， cytokine production， the T cell receptor signaling pathway， and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group， the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein （1.80%±0.67% vs 0.33%±0.13%， P<0.05） and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein （0.50%±0.09% vs 2.66%± 0.33%， P<0.001）. ConclusionThere is a reduction in the percentage of Tcf7⁺ T cells and an increase in the percentage of Cxcr6⁺ T cells in NASH mice， revealing the characteristics and differences of T cells in the liver of NASH mice.

ObjectiveTo understand the infection characteristics of multidrug-resistant organisms (MDROs) in hospitalized patients in a tertiary sentinel hospital in Shanghai, so as to provide an evidence for the development of targeted prevention and control measures. MethodsData of MDROs strains and corresponding medical records of some hospitalized patients in a hospital in Shanghai from 2021 to 2023 were collected, together with an analysis of the basic information, clinical treatment, underlying diseases and sources of sample collection. ResultsA total of 134 strains of MDROs isolated from hospitalized patients in this hospital were collected from 2021 to 2023 , including 63 strains of methicillin-resistant Staphylococcus aureus (MRSA), 57 strains of carbapenem-resistant Acinetobacter baumannii (CRAB), and 14 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP). Of the 134 strains, 30 strains were found in 2021, 47 strains in 2022 and 57 strains in 2023. The male-to-female ratio of patients was 2.05∶1, with the highest percentage (70.90%) in the age group of 60‒<90 years. The primary diagnosis was mainly respiratory disease, with lung and respiratory tract as the cheif infection sites. There was no statistically significant difference in the distribution of strains between different genders and infection sites (P>0.05). However, the differences in the distribution of strains between different ages and primary diagnosis were statistically significant (P<0.05). Patients who were admitted to the intensive care unit (ICU), had urinary tract intubation, were not artery or vein intubated, were not on a ventilator, were not using immunosuppresants or hormones, and were not applying radiotherapy or chemotherapy were in the majority. There was no statistically significant difference in the distribution of strains for whether received radiotherapy or chemotherapy or not (P>0.05), while the differences in the distribution of strains with ICU admission history, urinary tract intubation, artery or vein intubation, ventilator use, and immunosuppresants or hormones use or not were statistically significant (all P<0.05). The type of specimen was mainly sputum, the hospitalized ward was mainly comprehensive ICU, the sampling time was mainly in the first quarter throughout the year, the number of underlying diseases was mainly between 1 to 2 kinds, the application of antibiotics ≥4 kinds, and those who didn’t receive any surgery recently accounted for the most. There were statistically significant differences in the distribution of strains between different specimen types, wards occupied and history of ICU stay (P<0.05), but no statistically significant difference in the distribution of strains between different sampling times, number of underlying diseases and types of antibiotics applied (P>0.05). ConclusionThe situation of prevention and control on MDROs in this hospital is still serious. Focus should be placed on high-risk factors’ and infection monitoring and preventive measures should be strengthened to reduce the incidence rate of MDROs infection.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*