Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

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*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

New quality productive forces are advanced productive forces in line with the new development concept,with the characteristics of high technology,high efficiency and high quality.It has a guiding role in realizing the high-quality and sustainable development of public hospitals.Starting from the basic connotation of the new quality productivity,it studies the core elements and implementation paths of establishing a lean management system that meets the requirements of high-quality development of public hospitals from the perspective of the leap in the combination of labourers,labour materials,labour objects and their optimisation.Combined with the actual situation of Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine,the specific application path is discussed,in order to be able to achieve the transformation and upgrading of public hospitals to provide experience to learn from.

New quality productive forces are advanced productive forces in line with the new development concept,with the characteristics of high technology,high efficiency and high quality.It has a guiding role in realizing the high-quality and sustainable development of public hospitals.Starting from the basic connotation of the new quality productivity,it studies the core elements and implementation paths of establishing a lean management system that meets the requirements of high-quality development of public hospitals from the perspective of the leap in the combination of labourers,labour materials,labour objects and their optimisation.Combined with the actual situation of Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine,the specific application path is discussed,in order to be able to achieve the transformation and upgrading of public hospitals to provide experience to learn from.

Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the first-line treatment for advanced non-small cell lung cancer(NSCLC)in the population with tumor proportion score(TPS)≥1%of PD-L1,and provide some reference for the clinical use and future price negotiation of pembrolizumab.Methods Based on Pubmed database,the published RCT literatures of pembrolizumab were analyzed,and the survival data were extracted,combined with the treatment plan of a tertiary hospital,the Markov model were established to simulate the cost and health effectiveness of patients for twenty years,and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis.Results Twenty years later,the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/quality adjusted life month(QALM)and ￥41 213.08/QALM.Compared with the chemotherapy group,the incremental cost effective ratio(ICER)was ￥104 485.36/QALM.Conclusion When the willingness to pay(WTP)value was ￥30 902/QALM,the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy,and the sensitivity analysis showed that the results of the model were relatively stable.

[Abstract] [Objective] To analyze the detection ability of one imported and three domestic microcolumn agglutination anti-human globulin cards in unexpected antibody screening test. [Methods] A total of 104 positive samples from antibody screening test conducted at our hospital from July to September 2022 were selected. Microcolumn agglutination antiglobulin tests were performed in parallel with antibody screening tests using one imported card (A Card) and three domestic cards (B, C and D Cards ) to analyze the differences in the sensitivity, specificity and agglutination intensity scores. [Results] The sensitivity of the four anti-human globulin cards was as follows: D card 88.51% (131/148) > C card 83.22% (124/149) > B card 81.63% (120/147) > A card 80.54% (120/149); the specificity was A card 97.79% (133/136) > B card 95.65% (132/138) > D card 95.62% (131/137) > C card 93.38% (127/136); and the average agglutination intensity score (points) was D card 214.57 > C card 191.90 > A Card 179.69 > B Card 175.83, and the H value of Kruskal-Wallis test was 7.221, with no statistically significant difference (P > 0.05). Among them, C card was prone to false positives, accounting for 3.16% (9/285), and A card was prone to false negatives, accounting for 10.18% (29/285). [Conclusion] There were differences in the detection ability of anti-human globulin cards of different manufacturers, and some domestic cards have higher detection performance than imported cards. It is recommended to use anti-human globulin cards of two manufacturers routinely in clinical practice, that is, to use cards with high detection sensitivity for antibody screening tests to avoid antibody missed detection as much as possible, and to use cards with high specificity for cross-matching blood tests to avoid delays in transfusion due to false positives, which could hinder transfusion treatment.

Inborn errors of immunity (IEI) are immune system disorders caused by genetic mutations, often presenting with varying degrees of infection, immune dysregulation, lymphoproliferation, and tumor susceptibility. Initially, IEIs were typically diagnosed in patients with recurrent and unusual infections. However increasing research has shown that noninfectious manifestations can also be the initial or even primary presentation of IEI. Over the past ten years, more and more IEIs associated with autoinflammatory symptoms have been identified. Although these diseases are rare, relevant research suggests that immune deficiency and autoinflammation are not opposing conditions but rather interconnected aspects of the immune system, influencing each other in a complementary and inseparable manner. This article reviews the mechanisms involved in IEI with autoinflammation, and proposes some clues for identifying IEI manifested as autoinflammation. It also summarizes the current progress in the diagnosis and treatment of IEI manifested as autoinflammation, and presents prospects for future research on IEI.