Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: a meta-analysis of phase 3 clinical trials.

Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).

Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: An updated meta-analysis.

BACKGROUND: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68-0.94), PFS (HR = 0.78; 95% CI: 0.66-0.93), pCR (OR = 13.00; 95% CI: 7.82-21.61) and R0 resection (OR = 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26-4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63-1.08). CONCLUSIONS: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.

Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials.

Objective: Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results: This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common. Conclusion: This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Effects of nitrification and urease inhibitors on ammonia-oxidizing microorganisms, denitrifying bacteria, and greenhouse gas emissions in greenhouse vegetable fields.

Soil microorganisms and N cycling are important components of biogeochemical cycling processes. In addition, the study of the effects of nitrification and urease inhibitors on N and microorganisms in greenhouse vegetable fields is essential to reducing N loss and greenhouse gas emissions. The effects of nitrification inhibitors [2-chloro-6-(trichloromethyl) pyridine (CP), dicyandiamide (DCD)], and urease inhibitor [N-(n-butyl) thiophosphoric triamide (NBPT)] on soil inorganic N (NH4+-N, NO2--N and NO3--N) concentrations and the production rates of greenhouse gases (N2O, CH4, and CO2) in greenhouse vegetable fields were investigated via indoor incubation experiments. Polymerase chain reaction amplification and high-throughput sequencing technology (Illumina Miseq) were used to explore the community structure and abundance changes of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and denitrifying bacteria (nirK and nirS). The results showed that CP and DCD obviously inhibited NH4+-N conversion, and NO2--N, and NO3--N accumulation, NBPT slowed down urea hydrolysis and NH4+-N production, and the apparent nitrification rates of soil were in the following order: NBPT > DCD > DCD + NBPT > CP + NBPT > CP. Compared with urea treatment, the peak N2O production rate of inhibitor treatment decreased by 73.30-99.30%, and the production rate of CH4 and CO2 decreased by more than 66.16%. DCD and CP reduced the abundance of AOA and AOB, respectively. Furthermore, NBPT hindered the growth of ammonia-oxidizing microorganisms and nirS-type denitrifying bacteria, and urea and nitrification inhibitors were detrimental to the growth of Ensifer and Sinorhizobium in the nirK community. Nitrification and urease inhibitors can effectively slow down nitrification and greenhouse gas emissions, reduce N loss and improve soil quality by inhibiting the growth of ammonia-oxidizing microorganisms and denitrifying bacteria.

Pyrite and sulfur-coupled autotrophic denitrification system for efficient nitrate and phosphate removal.

The inefficiency of nitrogen removal in pyrite autotrophic denitrification (PAD) and the low efficiency of PO43--P removal in sulfur autotrophic denitrification (SAD) limit their potential for engineering applications. This study examined the use of pyrite and sulfur coupled autotrophic denitrification (PSAD) in batch and column experiments to remove NO3--N and PO43--P from sewage. The effluent concentration of NO3--N was 0.32 ± 0.11 mg/L, with an average Total nitrogen (TN) removal efficiency of 99.14%. The highest PO43--P removal efficiency was 100% on day 18. There was a significant correlation between pH and the efficiency of PO43--P removal. Thiobacillus, Thiomonas and Thermomonas were found to be dominant at the bacterial genus level in PSAD. Additionally, the abundance of Thermomonas in the PSAD was greater than that observed in the SAD reactor. This result indirectly indicates that the PSAD system has more advantages in reducing N2O.

Heterogeneous Electro-Fenton-Catalyzed Degradation of Rhodamine B by Nano-Calcined Pyrite.

The use of natural pyrite as a catalyst for the treatment of recalcitrant organic wastewater by an electro-Fenton system (pyrite-EF) has recently received extensive attention. To improve the catalytic activity of natural pyrite (Py), magnetic pyrite (MPy), and pyrrhotite (Pyr), they were obtained by heat treatment, and the nanoparticles were obtained by ball milling. They were characterized by X-ray diffraction, X-ray electron spectroscopy, and scanning electron microscopy. The degradation performance of rhodamine B (Rhb) by heterogeneous catalysts was tested under the pyrite-EF system. The effects of optimal pH, catalyst concentration, and current density on mineralization rate and mineralization current efficiency were explored. The results showed that the heat treatment caused the phase transformation of pyrite and increased the relative content of ferrous ions. The catalytic performance was MPy > Py > Pyr, and the Rhb degradation process conformed to pseudo-first-order kinetics. Under the optimum conditions of 1 g L-1 MPy, an initial pH of five, and a current density of 30 mA cm-2, the degradation rate and TOC removal rate of Rhb wastewater reached 98.25% and 77.06%, respectively. After five cycles of recycling, the chemical activity of MPy was still higher than that of pretreated Py. The main contribution to Rhb degradation in the system was •OH radical, followed by SO4•-, and the possible catalytic mechanism of MPy catalyst in the pyrite-EF system was proposed.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Characteristics and health risk assessment of heavy metal pollution in atmospheric particulate matter in different regions of the Yellow River Delta in China.

To understand the characteristics, temporal and spatial variation, and health risks of atmospheric heavy metal pollution in different areas of the YRD (Yellow River Delta), atmospheric particles samples were collected in the YRD in China during 2016-2017. A total of 10 monitoring points were chosen in different areas (industrial parks, main urban areas, and rural areas) in the YRD, heavy metals were monitored using atomic fluorescence spectrometry and graphite furnace atomic absorption spectrometry. The results showed that TSP (total suspended particulate), PM10 (particulate matter with an aerodynamic diameter less than 10 µm), and PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm) contents were higher in the Kenli EDZ (economic development zone) and Kenli urban areas than those in other points. The concentration range of heavy metals in atmospheric samples at 10 points was different, with a difference of five orders of magnitude, of which the content of copper (Cu) was the highest, with the highest concentration of 4.375 µg/m3, and the content of particulate mercury (Hg) was the lowest, with the minimum concentration of 0.00001 µg/m3. Among the nine heavy metals, the contents of cadmium (Cd), lead (Pb), and Hg were higher in winter than in summer, and chromium (Cr), nickel (Ni), Cu, and manganese (Mn) were higher in summer than in winter. In addition to Hg, the contents of the other eight heavy metals in particulate matter showed a trend that urban areas and EDZs had higher concentrations than cities and towns and nature reserves, which can be attributed to industrial activities and coal-fired fuel emissions. Health risk assessment was carried out for adults and children, respectively, and the results showed that carcinogens have no obvious carcinogenic risk, but As and Cr have major potential carcinogenic risk. Among the noncarcinogenic substances, Mn has the greatest noncarcinogenic risk, and urban areas and economic development zones have the greatest risk. This study investigated the characteristics and health risk assessment of atmospheric heavy metal pollution in different areas in the YRD to supplement the research contents of atmospheric particulate heavy metals in the YRD in domestics and overseas. It is also critical to study the pollution and migration of heavy metals in China.

A single-center randomized controlled study of intraperitoneal hyperthermic chemoperfusion in combination of recombinant human tumor necrosis factor (TNF) in treatment of malignant ascites caused by advanced abdominal cancers.

INTRODUCTION: Malignant peritoneal effusion is a common complication of advanced malignancies, which has a poor prognosis for patients. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used in the treatment of advanced gynecological tumors, especially ovarian cancer (OC). Relative studies have indicated that HIPEC allows for direct exposure of tumor cells to high peritoneal concentrations of cytotoxic drugs without increasing systemic toxicity compared with intravenous treatment. Recombinant human tumor necrosis factor for injection (rmhTNF-NC) is a safely tolerated immunotherapeutic drug that has becoming a mainstay of treatment for malignant effusions. Currently, a prospective study is required to determining the efficacy of rmhTNF-NC plus cisplatin for the treatment of malignant peritoneal effusion for OC. METHODS: Design and setting: This is a single-center, open trial will be performed in Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine. PARTICIPANTS: Eligible patients will be those with advanced gynecologic cancers and who would be suitable for HIPEC. INTERVENTION AND CONTROL: HIPEC with cisplatin and intraperitoneal perfusion with rmhTNF-NC. COINTERVENTIONS: Further chemotherapy will be offered to patients as per current practice.OutcomesPilot study: Patients and clinicians' acceptability of the trial to assist in optimization of recruitment.Primary outcome: One-year overall survival (OS).Secondary outcomes: Progression-free survival (PFS), adverse events.Follow-up: One-year follow-up for OS.Sample size: Twenty patients to demonstrate therapeutic effect of peritoneal effusion caused by OC. DISCUSSION: This trial will determine the effectiveness of HIPEC with cisplatin and intraperitoneal perfusion with rmhTNF-NC for advanced gynecologic cancers, and guide the optimal treatment for these patients.

Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review.

BACKGROUND: Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. CASE PRESENTATION: A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. CONCLUSIONS: Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

Case report: pathological complete response in an IIIB non-small cell lung cancer patient after preoperative neoadjuvant nivolumab therapy combined with chemotherapy.

RATIONALE: For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer. PATIENT CONCERNS: A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to "coughing for more than one month.". The patient had nothing of note in either his medical history or that of his family, and no history of smoking. DIAGNOSIS: The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery. INTERVENTIONS: The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21. OUTCOMES: The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR). LESSONS: In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.

Efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis of randomized controlled trials.

Background: The addition of endocrine therapy to salvage radiotherapy (SRT) is expected to further improve the prognosis of patients with biochemical recurrence of prostate cancer after radical prostatectomy (RP). The quantitative synthesis of clinical outcomes of SRT combined with endocrine therapy is limited. Whether salvage radiotherapy plus endocrine therapy remains inconclusive. We performed a systematic review and meta-analysis of existing randomized controlled trials to evaluate the efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy. Methods: A systematic search of PubMed, EMBASE, and the Cochrane library was performed for articles published between January 1, 2012 and October 10, 2022. Data were analyzed using Review Manager 5.4.1 (Cochrane Collaboration Software). Main outcome and measures included biochemical progression-free survival (bPFS), metastasis free survival (MFS), overall survival (OS), and Grade 3 or higher adverse events (3+AEs), including acute and late adverse events. Results: In this systematic review and meta-analysis, 4 randomized controlled studies enrolling 2731 male (1374 of whom received SRT combined with endocrine therapy and 1357 controls) met the inclusion criteria. SRT combined with endocrine therapy were related to significantly improve bPFS (HR=0.52; 95% CI: 0.46 0.59; p<0.00001) and MFS (HR=0.75; 95% CI: 0.64 0.88; p<0.001). Compared with SRT alone, the combination therapy tended to be associated with prolong OS (HR=0.83; 95% CI: 0.69-1.01; p=0.06), but not statistically significant. At early follow-up, the risk of acute AEs was comparable in the two groups (RR=1.04; 95% CI: 0.22-4.85). However, the risk of late AEs was higher in the combination group at later follow-up (RR=1.33; 95% CI: 1.09-1.62). Conclusions: This systematic review and meta-analysis found superior efficacy associated with adding endocrine therapy to SRT compared with SRT alone in patients with biochemical recurrence after RP. Additional endocrine therapy is safe and feasible for patients with biochemical recurrence after RP. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022365432).

NR4A2 may be a potential diagnostic biomarker for myocardial infarction: A comprehensive bioinformatics analysis and experimental validation.

Background: Myocardial infarction is a well-established severe consequence of coronary artery disease. However, the lack of effective early biomarkers accounts for the lag time before clinical diagnosis of myocardial infarction. The present study aimed to predict critical genes for the diagnosis of MI by immune infiltration analysis and establish a nomogram. Methods: Gene microarray data were downloaded from Gene Expression Omnibus (GEO). Differential expression analysis, single-cell sequencing, and disease ontology (DO) enrichment analysis were performed to determine the distribution of Differentially Expressed Genes (DEGs) in cell subpopulations and their correlation with MI. Next, the level of infiltration of 16 immune cells and immune functions and their hub genes were analyzed using a Single-sample Gene Set Enrichment Analysis (ssGSEA). In addition, the accuracy of critical markers for the diagnosis of MI was subsequently assessed using receiver operating characteristic curves (ROC). One datasets were used to test the accuracy of the model. Finally, the genes with the most diagnostic value for MI were screened and experimentally validated. Results: 335 DEGs were identified in GSE66360, including 280 upregulated and 55 downregulated genes. Single-cell sequencing results demonstrated that DEGs were mainly distributed in endothelial cells. DO enrichment analysis suggested that DEGs were highly correlated with MI. In the MI population, macrophages, neutrophils, CCR, and Parainflammation were significantly upregulated compared to the average population. NR4A2 was identified as the gene with the most significant diagnostic value in the immune scoring and diagnostic model. 191 possible drugs for the treatment of myocardial infarction were identified by drug prediction analysis. Finally, our results were validated by Real-time Quantitativepolymerase chain reaction and Western Blot of animal samples. Conclusion: Our comprehensive in silico analysis revealed that NR4A2 has huge prospects for application in diagnosing patients with MI.

Ablation Therapy Combined with EGFR TKIs in the Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3. RESULTS: A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: -2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: -2.80, 95% CI: 1.64 to 4.80, P< 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: -1.66, 95% CI: 1.20 to 2.31, P< 0.01), and disease control rate (DCR) (RR: -2.68, 95% CI: 1.41 to 5.06, P< 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone. CONCLUSION: Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.

Effective Treatment of NSCLC with Surgery After Nivolumab Combined with Chemotherapy: A Case Report and Brief Review of the Literature.

INTRODUCTION: Immuno checkpoint inhibitors (ICIs) including anti-PD-L1 antibody have shown certain therapeutic effects on various cancer types. Here, we reported a case of the patient with resectable non-small cell lung cancer (NSCLC) showing a complete response to nivolumab combined with chemotherapy. PATIENT INFORMATION: A 66-year-old male was diagnosed with stage IIIA large cell lung cancer, cT2N2M0, who was considered impossible to have a tumor resection due to his right hilar node enlargement. The diameter of the neoplasms was 22mm, and the patient wanted to get the chance of surgery. Light of all, surgery was the only radical treatment option and therefore planned. INTERVENTIONS: After administering 2 cycles of nivolumab combined with paclitaxel and cisplatin, the second chest computed tomography (CT) after the first scanning revealed the tumor apparent shrinking and vascular compression was disappeared than before. We performed a right upper lobectomy and mediastinal lymph node dissection. Pathologically, we confirmed no large cell lung cancer cells in the resected lung specimen. OUTCOMES: The follow-up showing that patient remains alive without recurrence to these days. CONCLUSION: This case report may provide a clue to the future development of induction therapy using nivolumab and surgery. The combined treatment of nivolumab and chemotherapy is likely to be considered as an optional management of resectable NSCLC.