BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Immune checkpoint inhibitors (ICIs) have become the cornerstone of treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC). However, resistance is inevitable, and the underlying mechanisms remain incompletely understood. Histological transformation is a rare but emerging cause of acquired resistance to immunotherapy, with only sporadic case reports documented to date. Here, we report the first case of lung adenocarcinoma that underwent histological transformation to atypical carcinoid following first-line therapy with ICIs combined with chemotherapy, highlighting the critical role of histological lineage switching in mediating NSCLC resistance to ICIs. Notably, the patient harbored a rearranged during transfection (RET) fusion mutation. Subsequent targeted therapy with Selpercatinib after histological transformation demonstrated favorable efficacy, suggesting a potential therapeutic strategy for atypical carcinoid patients with co-occurring rare driver mutations. This case provides a potential therapeutic option for atypical carcinoid patients with rare mutations.
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Humans ; Carcinoid Tumor/drug therapy* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Drug Resistance, Neoplasm ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy ; Lung Neoplasms/immunology* ; Oncogene Proteins, Fusion/genetics* ; Proto-Oncogene Proteins c-ret/genetics*

Epidermal growth factor receptor (EGFR) exon 20 mutations represent a rare subset of genetic alterations in non-small cell lung cancer (NSCLC). Among them, the complex mutation H773_V774delinsLM is exceedingly uncommon, accounting for only 0.2%-1% of all EGFR mutations. It is currently believed that rare EGFR mutations are generally resistant to the first- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although the third-generation EGFR-TKIs have shown some efficacy in certain rare mutations, clinical evidence regarding their use in NSCLC patients with the H773_V774delinsLM mutation remains sparse, and their efficacy and safety are yet to be clarified. Here, we present the first documented case of a patient with EGFR H773_V774delinsLM-mutant lung adenocarcinoma who experienced remarkable tumor regression following treatment with furmonertinib. This case highlights the potential utility of furmonertinib in treating patients with this rare EGFR mutation and may provide valuable insight into emerging treatment strategies for similarly affected patients.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Exons/genetics* ; Lung Neoplasms/enzymology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

Growth factors (GFs) are a class of peptides that facilitate cell growth by binding to specific receptors on the cell membrane. With unique properties, GFs are widely applied in the repair of injured tissue. To address the limitations associated with natural peptide-based GFs and recombinant GFs, researchers have developed diverse GF mimetics. This article offers a comprehensive review on common types of GFs and their applications in tissue repair and summarizes the features of GF mimetics currently under development. The aim is to provide valuable references for promoting the application of GFs in regenerative medicine.
Intercellular Signaling Peptides and Proteins/therapeutic use* ; Humans ; Tissue Engineering/methods* ; Regenerative Medicine/methods* ; Animals ; Wound Healing/drug effects* ; Biomimetic Materials

Objective:This study aims to explore the connotation and importance of clinical research infrastructure, elucidate the key points and operational models of clinical research wards, and summarize the experiences and practices of clinical research wards at Peking Union Medical College Hospital.Methods:The study employed on-site investigations and literature reviews to analyze the construction models and key features of clinical research wards in various medical institutions.Results:Additionally, it introduced advanced experiences from foreign centers and examined the challenges encountered during the process.Conclusions:As a phased achievement, it presents the experience and practices of Peking Union Medical College Hospital in constructing and operating clinical research wards based on National Facility for Translational Medicine (PUMCH). The construction of clinical research facilities and clinical research wards should focus on facility positioning, talent pool, financial investment, management operation, and information systems. This study provides references for the future construction, operation, and development of clinical research facilities.

Objective:To analyze the health development plans of the provinces in China during the " 14th Five-Year Plan" , and explore the key tasks, similarities and differences of health informatization construction in each province.Methods:Using the website of local people′s government and the official website of the provincial Health Commission, 27 copies of health development plans of various provinces during the " 14th Five-Year Plan" period were retrieved and collected from February 16 to June 5, 2022. The relevant statements of health information in the plan were extracted, content analysis was used to reveal the structural characteristics of the policy in the form of word frequency statistics, and discourse analysis was used to study the policy content.Results:The health information policies of 27 provinces during the " 14th Five-Year Plan" period could be summarized as 10 major themes, such as accelerating the construction of hierarchical diagnosis and treatment system, promoting the high-quality development of public hospitals, and deepening the reform of medical security system. The health information policy in the eastern, central and western regions was relatively clear, and there were certain differences in the construction points according to their own characteristics.Conclusions:During the " 14th Five-Year Plan" period, the policies of each province around the field of health information are well defined, and the core structure and content are similar. The distribution of key points in the eastern region is relatively balanced; the construction of health information in the central region is more prioritized and prominent; the construction of health information in the western region is focused on complementing the weak links and weaknesses.

Neurofibromatosis (NF) is a genetic disease in which the lungs are rarely involved. However, in NF cases with lung involvement, chest computed tomography may show bilateral basal reticulations, apical bullae, and cysts without bronchiectasis. Herein, we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis. Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough, sinusitis, and sperm quality decline, we considered the possibility of primary ciliary dyskinesia (PCD). Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD. Therefore, for patients with NF, when an image change exists in the lungs that does not correspond to NF, the possibility of other diagnoses, including PCD, must be considered.
Cilia ; Humans ; Kartagener Syndrome/genetics* ; Microscopy, Electron ; Mutation ; Neurofibromatosis 1/genetics*

BACKGROUND: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. METHODS: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. RESULTS: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). CONCLUSIONS Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.

BACKGROUND: The lack of pathological quality control standard in detecting epidermal growth factor receptor (EGFR) gene mutation in malignant pleural effusion leads to confusion in the interpretation of detection results and the clinical use of EGFR-tyrosine kinase inhibitor (TKI). Therefore, it is very important to propose quality control standards and guide the detection of EGFR mutation in pleural effusion. The aim of this study is to retrospectively analyze the results of EGFR gene mutation in pleural effusion sediment section according to strict pathological quality control standards, and the therapeutic effect of EGFR-TKIs guided by this detection results. METHODS: From January 2012 to June 2018, the clinical data of patients with pleural effusion collected from Department of Pathology of Peking Union Medical College Hospital were analyzed retrospectively. Among them, 132 patients with relatively complete clinical data and with EGFR gene mutation detection of paraffin-embedded pleural effusion sediment section according to the established quality control standard were included. According to the results of EGFR gene mutation, it was divided into positive group and negative group, and the efficacy of EGFR-TKIs in different groups was compared. RESULTS: After the centrifugation of pleural effusion, the sediment was embedded in paraffin, sectioned, and observed under the microscope after HE staining. If the number of tumor cells ≥100, it met the pathological quality control standard, and it could be used for subsequent EGFR gene mutation detection. EGFR gene mutations were detected in 72 (54.5%) of 132 patients. EGFR-TKIs were used in 69 of 72 mutation positive patients. Of 60 EGFR mutation negative patients, only 15 used EGFR-TKIs. In EGFR mutation positive group, the disease control rate (DCR) was 95.8%, and the median progression-free survival (PFS) was 11 months. In EGFR mutation negative group, the DCR was 0%, and the median PFS was 1 month. The DCR and PFS were significantly different between the two groups (P<0.05). CONCLUSIONS According to the pathological quality control standards, the embedded section of pleural fluid sediment can be used to detect EGFR gene mutation, and the results can be used to guide the clinical use of EGFR-TKIs.

The outbreaks of severe acute respiratory syndrome (SARS) in February 2003 in Guangdong, China, middle east respiratory syndrome (MERS) in September2012 in Kingdom of Saudi Arabia, and the current COVID-19 pandemics in December 2019 in Wuhan, China, are all caused by coronaviruses, and patients primarily died of acute respiratory distress syndrome (ARDS). Compared with more than 5 years of wreaking havoc from MERS-CoV and Ebor, China successfully contains the SARS-CoV within one year, which shows her advantages in political governance controlling such pandemics. Many coronaviruses have been separated and their molecular structures analyzed. However, there is no specific anti-coronavirus drug developed in the world since the outbreaks. The problems come from not only pharmaceutical technology per se that must treat both coronaviruses and their life-threatening ARDS, but also the small size of patients who could immune against the coronaviruses after infections resulting in pharmaceutical reluctance to invest in the area. Facing both the pharmaceutical and social-economic bottlenecks, here, we summarized the current development of anti-coronavirus drugs, and proposed the strategies of repurposing existing drugs and preparing their pharmacological combinations to fight the viruses including COVID-19 based on a well-understanding of how the coronaviruses enter the host and damage our respiratory system.