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*

Programmed cell death 1 (PD-1) inhibitor therapy for lung adenocarcinoma may induce rare but severe hematologic adverse events, including severe anemia. Although glucocorticoids are recommended for managing immune-related adverse events, therapeutic experience with PD-1 inhibitor-induced severe anemia remains limited, and its efficacy and safety have not been fully validated. This article reports a case of advanced lung adenocarcinoma in which severe anemia developed following combination therapy with chemotherapy and PD-1 inhibitor. After comprehensive evaluation, the patient was diagnosed with anemia of inflammation (AI) and achieved significant hemoglobin recovery following high-dose glucocorticoid treatment. These findings may provide new insights into the recognition and management of this rare hematologic toxicity in clinical practice.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Anemia/etiology* ; Immunotherapy/adverse effects* ; Lung Neoplasms/immunology* ; Male ; Antibodies, Monoclonal/therapeutic use* ; Middle Aged

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*

Objective:To investigate the impact of " staging" hybrid coronary artery revascularization (HCR) on the short-and long-term efficacy of patients with multiple coronary artery lesions.Methods:A retrospective case-control study was conducted. Eighty patients with multiple coronary artery lesions admitted to the Baoding Second Central Hospital from January 2017 to October 2018 were selected and divided into two groups according to different surgical methods. Forty patients were treated with " staging" HCR and were designated as the HCR group, and 40 patients were treated with off-pump coronary artery bypass grafting (OPCAB) and were designated as the OPCAB group. The perioperative related indicators and perioperative serious complications were compared between the two groups. The serum myocardial injury marker levels were detected preoperatively and 48 hours postoperatively, including heart-type fatty acid binding protein (H-FABP) and troponin I (cTnI). All subjects were followed up for at least 3 years to calculate the incidence of major adverse cardiovascular and cerebrovascular events (MACCE).Results:The bypass surgery time, mechanical ventilation time, ICU stay time, and total hospital stay time in the HCR group were all less than those in the OPCAB group (all P<0.05), and the incision length in the HCR group was shorter than that in the OPCAB group ( P<0.05). The intraoperative bleeding volume, postoperative 24-hour drainage volume, red blood cell transfusion volume, and plasma transfusion volume in the HCR group were all less than those in the OPCAB group (all P<0.05). Forty-eight hours after surgery, the serum H-FABP and cTnI levels in both groups were significantly higher than those preoperatively (all P<0.05), but the increase was more significant in the OPCAB group (all P<0.05). The perioperative serious complication rate in the HCR group was 2.50%(1/40), which was significantly lower than that in the OPCAB group [20.00%(8/40)] ( P<0.05). During the 3-year follow-up after surgery, the MACCE incidence in the HCR group was 12.50%(5/40), and that in the OPCAB group was 22.50%(9/40). There was no significant difference in the long-term MACCE incidence between the two groups ( P>0.05). Conclusions:" Staging" HCR treatment for multiple coronary artery lesions can achieve ideal surgical results. Compared with OPCAB, its short-term efficacy is more significant, and long-term efficacy is equivalent.

Objective:Due to the circumstances where people being required to home quarantine and eye hospitals being unable to receive patient normally, The application of internet plus technology is explored to build Remote Dedicated Doctor Platform of Ophthalmology (RDDPO) for online consultation, accessing to medication, medical services and advises orderly, and to help to further develop and apply the platform.Methods:In 2018, RDDPO was jointly developed.It has been modified and improved to the formulation of national medical policy and medical insurance policy and the outbreak of COVID-19 at the end of 2019, and it has been carried out comprehensive application verification during the prevention and control of COVID-19 epidemic.With a B/S structure, platform docks the official accounts of Wechat platform.On the server side, three J2EE frameworks of the integrated development, including Struts2, Spring and Hibernate are adopted; on the mobile client side, a combination of development tools including React-Native and Redux is used.Meanwhile, a micro-services Architecture (msA) of RESTful WebAPI is chosen at the business logic layer.The terminal data information is used to summarize the results of the platform's functional services for ophthalmic patients, such as remote diagnosis and treatment, online prescription, medicine delivery and health education, etc., and to make statistics on all kinds of data during the epidemic prevention and control period, so as to verify the operations management capabilities of the platform's functions.Results:During the period of COVID-19 epidemic prevention and control, the number of monthly visits of RDDPO increased from 1063 person times from September 1, 2019 to the end of September to 30 002 person times from February 1, 2020 to February 28, 2020.The proportion of diagnosis and treatment person times of this platform in the total number of diagnosis and treatment person times increased from 19.1% (203/1 063) to 92.3% (277/3 002), which can effectively avoid the risk of personal contact infection and meet the patients' medical needs.95.8% of the patients were very satisfied.95.8% of the patients were very satisfied.Conclusions:The RDDPO establishes a channel for doctor-patient communication during the epidemic, which can be considered as an important way to effectively address the needs of patients for medical treatment.

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.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and genetic susceptibility and is one of the chronic liver diseases that threaten human health .Under certain conditions, Th17 cells and regulatory T (Treg) cells can be transformed to each other to maintain immune homeostasis.In recent years, more and more studies have been performed on the involvement of Th 17 and Treg cells in the development and progression of liver diseases .Th17 cells, Treg cells, and their balance may become the new targets for the treatment of NAFLD.This article reviews the latest research advances in the association of Th 17 and Treg cells with NAFLD and the role of Th17/Treg balance in the development and progression of NAFLD .

Objective To prepare naloxone hydrochloride nasal spray and evaluate the ciliotoxicity and pharmacokinetics of the formulation. Methods The stability of naloxone hydrochloride was studied in pH3.5-5.5. Penetration promoting effects of absorp-tion enhancers on the naloxone hydrochloride were evaluated. Nasal ciliotoxicity studies were carried out using isolated toad palate. Rats were treated with naloxone hydrochloride solution by intramuscular injection of nasal drops to evaluate the pharmacokinetics. Results Naloxone hydrochloride solution was stable in pH3.5-5.5. Disodium ethylenediaminetetraacetic acid(0.2%,W/V)had the best penetration promoting effect on naloxone hydrochloride. Naloxone hydrochloride nasal spray did not exhibit obvious nasal ciliotox-icity compared to the negative control. The nasal spray had a faster therapeutic effect and its bioavailability was similar to that of the in-tramuscular injection. Conclusion Naloxone hydrochloride nasal spray prepared in this research is stable with no obvious nasal cilio-toxicity,has faster therapeutic effect,and good bioavailability,so may have a broad application prospect.

Objective To observe the effects of mild hypothermia on the myocardial mitochondrial injury induced by oxidative stress after restoration of spontaneous circulation (ROSC) in rat of cardiac arrest model.Methods Eighteen male Wistar rats were randomly (raudom number) divided into normal temperature group and mild hypothermia group after ROSC.Ultrasound was used to measure the left ventricular ejection fraction (EF),shortening fraction (FS) and stroke volume (SV).The levels of glutathione (GSH),malondialdehyde (MDA) and adenosine triphosphate (ATP) in myocardium were detected.The ultramicroscopic structure of myocardial mitochondria was observed under transmission electron microscope at 4 h after ROSC.Results There were no significant differences in basic life support (BLS) time,dosage of epinephrine and number of defibrillation attempt between two groups (P ＞ 0.05).The concentrations of GSH and ATP in myocardium of rats in hypothermia group were significantly higher than those in normal temperature group,while the level of MDA was significantly lower in hypothermia group than that in normal temperature group.Echocardiographic findings showed that hypothermia could significantly improve the EF,FS and SV after ROSC.The hypothermia decreased the myocardial mitochondria injury rather than normothermia [mitochondrial injury score:(0.21-±0.04) vs.(0.42 ±0.08),P ＜ 0.05].Conclusions In this model,mild hypothermia can decrease myocardial oxidative stress injury,improving the cardiac function after ROSC.