Current status and progress of PD-L1 detection: guiding immunotherapy for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths and represents a substantial disease burden worldwide. Immune checkpoint inhibitors combined with chemotherapy are the standard first-line therapy for advanced NSCLC without driver mutations. Programmed death-ligand 1 (PD-L1) is currently the only approved immunotherapy marker. PD-L1 detection methods are diverse and have developed rapidly in recent years, such as improved immunohistochemical detection methods, the application of liquid biopsy in PD-L1 detection, genetic testing, radionuclide imaging, and the use of machine learning methods to construct PD-L1 prediction models. This review focuses on the detection methods and challenges of PD-L1 from different sources, and discusses the influencing factors of PD-L1 detection and the value of combined biomarkers. Provide support for clinical screening of immunotherapy-advantage groups and formulation of personalized treatment decisions.

The combination of tumor mutational burden and T-cell receptor repertoire predicts the response to immunotherapy in patients with advanced non-small cell lung cancer.

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression-free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = -0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.

Genome-wide identification of ATG genes and their expression profiles under biotic and abiotic stresses in Fenneropenaeus chinensis.

BACKGROUND: Autophagy is a conserved catabolic process in eukaryotes that contributes to cell survival in response to multiple stresses and is important for organism fitness. Extensive research has shown that autophagy plays a pivotal role in both viral infection and replication processes. Despite the increasing research dedicated to autophagy, investigations into shrimp autophagy are relatively scarce. RESULTS: Based on three different methods, a total of 20 members of the ATGs were identified from F. chinensis, all of which contained an autophagy domain. These genes were divided into 18 subfamilies based on their different C-terminal domains, and were found to be located on 16 chromosomes. Quantitative real-time PCR (qRT-PCR) results showed that ATG genes were extensively distributed in all the tested tissues, with the highest expression levels were detected in muscle and eyestalk. To clarify the comprehensive roles of ATG genes upon biotic and abiotic stresses, we examined their expression patterns. The expression levels of multiple ATGs showed an initial increase followed by a decrease, with the highest expression levels observed at 6 h and/or 24 h after WSSV injection. The expression levels of three genes (ATG1, ATG3, and ATG4B) gradually increased until 60 h after injection. Under low-salt conditions, 12 ATG genes were significantly induced, and their transcription abundance peaked at 96 h after treatment. CONCLUSIONS: These results suggested that ATG genes may have significant roles in responding to various environmental stressors. Overall, this study provides a thorough characterization and expression analysis of ATG genes in F. chinensis, laying a strong foundation for further functional studies and promising potential in innate immunity.

Lipidomics study of Liujunzi decoction in hyperlipidemia rats with spleen deficiency based on UPLC-Q-TOF/MS.

Hyperlipidemia refers to the abnormal levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in peripheral blood circulation. It is a predominant risk factor underlying cardiovascular and cerebrovascular diseases, including coronary heart disease and atherosclerosis. Furthermore, it is also one of the most prevalent chronic diseases globally. Liujunzi Decoction is the basic prescription for the treatment of spleen and stomach diseases. It can tonify the spleen and qi, remove dampness, and reduce turbidity. Moreover, it is also clinically used for the treatment of spleen deficiency hyperlipidemia. However, its metabolites and therapeutic effect on spleen deficiency hyperlipidemia have not been comprehensively determined in vitro and in vivo. This study established a rat model of spleen deficiency hyperlipidemia by inducing starvation and satiety disorders, exhaustion swimming, and intragastric administration of the fat emulsion. To identify related metabolite changes and serum lipid composition, UPLC-Q-TOF-MS, PCA, and OPLS-DA lipidological methods were performed. The results demonstrated significant changes in rat's signs during the modeling process, which were consistent with the criteria for the syndrome differentiation of spleen deficiency in traditional Chinese medicine. Furthermore, this study identified 100 potential biomarkers in rat serum, of which 52 were associated with lipid synthesis, such as LPC, PC, PI, PE, PA, Cer, SM, etc. The pathways involved were glycerol phospholipid, sphingomyelin, and glycerol ester metabolisms. After the Liujunzi decoction intervention, 56 potential biomarkers were observed in the high-dose group, alleviating the metabolic spectrum imbalance by reducing metabolite levels. In addition, metabolic pathway disturbances were markedly improved. This study provides references for future studies on Liujunzi decoction and furnishes essential data for assessing the relationships between chemical constituents and pharmacological activities of Liujunzi decoction.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study.

BACKGROUND: The combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy. METHODS: Eligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6-20.4) and 80.0% (95% CI, 64.4-90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1-7.5), and the median OS was 12.1 months (95% CI, 9.1-16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9-65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%). CONCLUSION: Camrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Efficacy of targeted therapy in patients with non-small cell lung cancer harboring very rare mutations in EGFR exon 18.

Background: Somatic mutations in epidermal growth factor receptor (EGFR) exon 18 are classified as uncommon or rare mutations in non-small cell lung cancer (NSCLC), in this context, other than G719X or E709X exon 18 mutations are even more rare and heterogeneous. In such scenario, first line treatment options are still debated. The aim of this study was to investigate the response of NSCLC patients harboring very rare exon 18 mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Methods: This retrospective descriptive study included 105 patients with NSCLC harboring mutations in EGFR exon 18 diagnosed at West China Hospital. The clinical response to EGFR-TKIs was evaluated according to different classifications of mutations in 45 NSCLC patients: 39 harboring G719X or E709X mutations and 6 harboring very rare mutations in EGFR exon 18. Results: Among 105 patients, 84% (88/105) harbored rare mutations in EGFR exon 18, including G719X and E709X mutations. The remaining 16% (17/105) had very rare mutations in EGFR exon 18, including E709_710delinsX and G724S. For the subsequent efficacy analysis of EGFR-TKI in 45 NSCLC patients, patients harboring very rare mutations achieved a favorable disease control rate (DCR) of 100% and had a median progression-free survival (PFS) of 17.2 months, which was not significantly different compared to patients harboring G719X or E709X (P=0.59). Conclusions: EGFR-TKIs showed great efficacy in terms of responses and survival in patients harboring exon 18 EGFR rare mutations. This may justify the use of targeted therapies as a potential treatment strategy for these patients.

Efficacy and Safety of Acupuncture for Restless Legs Syndrome in Patients with End-Stage Renal Disease: A Randomized-Controlled Trial at Hospital-Based Hemodialysis Center.

Background: Restless legs syndrome (RLS) is frequent in patients with hemodialysis (HD) and occurs predominantly in its most severe forms. The study was conducted to evaluate the efficacy and safety of acupuncture for RLS in patients with end-stage renal disease (ESRD) at hospital-based HD center. Methods: This single-blind, randomized controlled trial was performed on patients with HD and RLS who were randomly assigned to the experimental group and control group. Data were collected using the International Restless Legs Syndrome Rating Scale (IRLSRS), Insomnia Severity Index (ISI), and heart rate variability (HRV) records at baseline, after the therapeutic course (12 times/4 weeks), and 1-week follow-up. Result: A total of 47 patients were evaluated with IRLSRS score from 11 to 30 in this study. There were 41 patients enrolled in the study based on inclusion/exclusion criteria and allocated randomly into two groups. A total of 35 participants completed the trial, including 18 subjects in the experimental group and 17 subjects in the control group. The comparison of IRLSRS and ISI showed a significant reduction between two groups after acupuncture treatment (p = 0.002, p = 0.003). The ISI after 1-week follow-up also revealed significant decrease (p = 0.003). This HRV results showed that high frequency (HF%) increased significantly (p = 0.021) and low frequency (LF%) decreased significantly in the acupuncture group (p = 0.021). The generalized estimating equation showed that the IRLSRS improved by 2.902 points (p < 0.001) in the acupuncture group compared with the control group and by 1.340 points (p = 0.003) after 1-week follow-up. There were no adverse effects observed during HD in this study. Discussion: The authors conclude that acupuncture could effectively improve the symptoms of RLS significantly. The results from this study provide clinical evidence on the efficacy and safety of acupuncture to treat the patients with RLS at the HD center.

Smart Solid-State Interphases Enable High-Safety and High-Energy Practical Lithium Batteries.

With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all-in-one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch-type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid-state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3-4.5 V), the pouch-type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self-generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch-type cells are attributed to the robust and stable anion-induced electrode-electrolyte interphases and local solid-state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high-performance batteries.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

A deep-learning-based genomic status estimating framework for homologous recombination deficiency detection from low-pass whole genome sequencing.

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0.980 in simulated low-pass WGS data, and obtained a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 1.3 × 10-4, compared with BRCA-intact samples). In ovarian cancer, GSscan obtained higher HRD risk scores in BRCA-deficient samples in both simulated data and clinical samples (p = 2.3 × 10-5 and p = 0.039, respectively, compared with BRCA-intact samples). Moreover, HRD-positive patients predicted by GSscan showed longer progression-free intervals in TCGA datasets (p = 0.0011) treated with platinum-based adjuvant chemotherapy, outperforming existing low-pass WGS-based methods. Furthermore, GSscan can accurately predict HRD status using only 1 ng of input DNA and a minimum sequencing coverage of 0.02 × , providing a reliable, accessible, and cost-effective approach. In summary, GSscan effectively and accurately detected HRD status, and provide a broadly applicable framework for disease diagnosis and selecting appropriate disease treatment.

First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial.

BACKGROUND: The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial. METHODS: Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile. RESULTS: Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1-49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator. CONCLUSION: Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT04346381.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Joint application of metagenomic next-generation sequencing and histopathological examination for the diagnosis of pulmonary infectious disease.

IMPORTANCE: The diagnosis of some pulmonary infectious diseases and their pathogens is very difficult. A more precise diagnosis of pulmonary infectious diseases can help clinicians use proper antibiotics as well as reduce the development of drug-resistant bacteria. In this study, we performed both mNGS and pathology on lung puncture biopsy tissue from patients and found that combined mNGS and histopathology testing was significantly more effective than histopathology testing alone in detecting infectious diseases and identifying infectious diseases. In addition, the combined approach improves the detection rate of pathogenic microorganisms in infectious diseases and can be used to guide precision clinical treatment.

The clinical features and prognosis of fungal pleural infection: A case series and literature review.

Fungal pleural infections are infrequent and insidious, for which there are neither large clinical studies nor targeted guidelines to provide standardized treatment options. We reported 4 cases of fungal pleural infection and reviewed the cases of fungal pleural infections in previous studies to provide a basis for the diagnosis and treatment of fungal pleural infections. There were 2 females and 2 males with a mean age of 58.5 years in our data. The average time from onset to diagnosis was 30.25 days. Risk factors most frequently included pulmonary diseases (n = 4) and malignancy (n = 1). Two patients underwent pleural biopsy through a thoracoscope, and no pathogens were detected. Pleural fluid culture was positive in 2 out of 3 cases. The diagnoses were "possible" (n = 1), "probable" (n = 1), and "proven" (n = 2). All patients received systemic antifungal therapy, and 3 received combined thoracic drainage. The outcomes were cured (n = 1), improved (n = 2) and lost to follow-up (n = 1). We reviewed 12 cases of fungal pleural infection in previous studies. The diagnosis was confirmed via culture in 7 cases and via biopsy in 8 cases. The pathogen was Aspergillus in 7 cases. After a combination of systemic antifungal (n = 12) and local treatment (n = 11), 10 patients improved and 2 patients died. Diagnosis of fungal pleural infection should incorporate risk factors, clinical presentation and fungal evidence, with pleural fluid culture being an important and feasible mean of confirming the diagnosis; and treatment should be based on systemic antifungal therapy supplemented by topical therapy.

Acupuncture for ventilator-dependent patients at a hospital-based respiratory care center: A randomized controlled trial.

Background: In intensive care units, mechanical ventilation is an important therapy to help patients with dyspnea. However, long-term ventilator dependence would consume huge medical resources and increase the risk of morbidity and mortality. The aim of the study was to examine the efficacy of the acupuncture combined with western medical care on ventilator parameters in ventilator-dependent patients. Methods: In this clinical trial, 80 ventilator-dependent patients aged 20 to 80 years old were randomly assigned to acupuncture group and control group in the respiratory care center (RCC) of Changhua Christian Hospital. Besides regular medical care and therapy, participants in the acupuncture group received acupuncture therapy at the same 17 acu-points for 20 minutes once a day, a total of 12 sessions. The ventilator parameters were recorded to evaluate the respiratory efficiency for all participants. The primary outcome was rapid shallow breathing index (RSBI), and secondary outcomes were respiratory rate (RR), tidal volume (TV) and ventilation per minute (MV). Results: Though there was no significant difference in the parameter between the acupuncture group and the control group, we found the trend of decreasing RSBI in the acupuncture group. In subgroup analyses, the mean of RSBI significantly decreased 16.02 (with the SD in 60.84) in acupuncture group, while it increased 17.84 (with the SD in 39.38) in control group (p=0.036) after 12 sessions. Conclusion: Acupuncture treatment can improve breathing ability of patients with respirator dependence in respiratory care center.

Superior clinical outcomes in patients with non-small cell lung cancer harboring multiple ALK fusions treated with tyrosine kinase inhibitors.

Background: Patients with non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) fusions may benefit from ALK-tyrosine kinase inhibitors (ALK-TKIs). However, few studies have analyzed the clinical outcome in patients harboring multiple ALK fusions, including double or triple ALK fusions. Here, our study aimed to analyze the impact of harboring multiple ALK fusions on the efficacy of receiving ALK-TKIs in NSCLC patients. Methods: A total of 125 patients with ALK-rearranged NSCLC detected by targeted capture DNA-based next-generation sequencing (NGS) at West China Hospital were enrolled. The literature on patients harboring multiple ALK fusions was systematically reviewed. The clinical response to ALK-TKIs was evaluated according to ALK fusion patterns in 62 patients: 56 from our center and 6 from the literature. Results: Among the 125 patients, a single canonical echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion was detected in 65.6% (82/125), a single non-EML4-ALK fusion was detected in 13.6% (17/125), and multiple ALK fusions were detected in 20.8% (26/125). Among the 62 patients with ALK fusion treated with ALK-TKIs, the median progression-free survival (PFS) was significantly longer in patients with multiple ALK fusions than in those with a single ALK fusion (26.9 vs. 11.2 months, P=0.009), irrespective of brain metastasis, type of TKI drug, and treatment lines. The multiple ALK fusion group also tended to have a longer overall survival (OS) (P=0.26). Multivariate Cox regression analysis revealed that harboring multiple ALK fusions had the potential to be an independent predictor of better PFS for ALK-positive NSCLC [hazard ratio (HR) =0.490; 95% confidence interval (CI): 0.229-1.049]. Conclusions: Harboring multiple ALK fusions could serve as an independent predictive marker of better clinical outcome for patients with NSCLC and ALK rearrangement who have received ALK-TKIs treatment.