Efficacy of Hepatoprotective Formula, Entecavir, and Continuous Nursing in Patients with Hepatitis B Cirrhosis.

Objective: This study aimed to assess the efficacy of combining a hepatoprotective formula with entecavir and continuous nursing in improving treatment outcomes for patients with hepatitis B cirrhosis. Methods: This study included 80 patients with hepatitis B cirrhosis admitted to our hospital from March 2021 to December 2022. These patients were randomly divided into an experimental group and a control group, with 40 patients in each group. Patients in the experimental group received a hepatoprotective formula consisting of Astragalus membranaceus, Salvia miltiorrhiza, Schisandra chinensis, and Glycyrrhiza uralensis, along with the antiviral drug entecavir and continuous nursing, while patients in the control group received only entecavir and routine care. Outcome measures during the study included clinical efficacy, liver function indicators (ALT, AST), coagulation function indicators (PT, TT), traditional Chinese medicine syndrome scores (to track changes in symptoms like rib pain and abdominal distension), treatment compliance, and quality of life. These measures provided a comprehensive assessment of the therapeutic effects, covering both Western medical and traditional Chinese medicine perspectives. Results: The total effective rate in the experimental group was 92.5%, significantly higher than the 77.5% in the control group (P < .05). Liver function significantly improved in the experimental group, with mean ALT decreasing from 128.4 U/L at baseline to 49.2 U/L after treatment, and mean AST decreasing from 102.6 U/L to 41.8 U/L (both P < .01). Coagulation function also showed greater improvements, with mean PT decreasing from 19.2 s to 14.8 s and mean TT decreasing from 22.4 s to 17.5 s in the experimental group (both P < .01), compared to more modest changes in the control group. Traditional Chinese medicine syndrome scores for rib pain and abdominal distension decreased by 75% and 80% respectively in the experimental group, indicating significant relief of these symptoms. Patient treatment compliance was 95% in the experimental group versus 82% in the control group. Quality of life scores improved by 28% in the experimental group compared to 15% in the control group. Conclusion: This study demonstrates that a comprehensive treatment approach combining a traditional Chinese medicine-based hepatoprotective formula with Western antiviral therapy and continuous nursing care can provide significantly greater benefits for patients with hepatitis B cirrhosis compared to antiviral therapy alone. The experimental group showed superior outcomes across multiple measures, including liver function, coagulation status, traditional Chinese medicine symptom scores, treatment compliance, and quality of life. These findings suggest that integrating a herbal hepatoprotective formula into the standard of care for hepatitis B cirrhosis may be a valuable strategy to improve clinical outcomes and patient well-being. Further research is warranted to validate these results and explore the underlying mechanisms by which this comprehensive approach exerts its hepatoprotective effects. Implementing this combined treatment protocol has the potential to optimize the management of hepatitis B cirrhosis in clinical practice.

Comprehensive analysis of T cell receptor repertoire in patients with KRAS mutant non-small cell lung cancer.

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in non-small cell lung cancer (NSCLC). The administration of immunotherapy has demonstrated significant efficacy in prolonging the overall survival of patients with KRAS mutation in recent years. However, the efficacy of immunotherapy in KRAS mutant NSCLC is variable. Analysis of T cell receptor (TCR) repertoire may contribute to a better understanding of the mechanisms behind such differential outcomes. Methods: A total of 47 patients with KRAS mutant NSCLC were enrolled in this study. Deep sequencing of the TCR ß chain complementarity-determining regions in tumor tissue and paired peripheral blood specimens was conducted. Comprehensive analysis of TCR repertoire metrics was performed with different KRAS mutation subtypes and concomitant mutations. Moreover, the associations between TCR repertoire metrics and tumor mutation burden (TMB), as well as programmed death-ligand 1 were explored, respectively. Results: TCR repertoire metrics, including Shannon index, Clonality, and Morisita index (MOI), showed no significant differences among different KRAS mutation subtypes. The similar results were observed between patients with tumor protein p53 (TP53) mutation and those with wild-type TP53. In contrast, although no significant differences were found in Shannon index and Clonality, patients with KRAS/serine/threonine kinase 11 (STK11) comutation showed a significantly higher MOI compared to their STK11 wild-type counterparts (P=0.012). In addition, TCR repertoire metrics were neither associated with TMB nor programmed death-ligand 1 expression in KRAS mutant NSCLC. Conclusions: This retrospective study comprehensively described the TCR repertoire in KRAS mutant NSCLC. A higher MOI represented more overlap of the TCR repertoire between tumor tissue and paired peripheral blood, indicating distinctive immunological features in NSCLC with KRAS/STK11 comutation.

Detection of Potential Mutated Genes Associated with Common Immunotherapy Biomarkers in Non-Small-Cell Lung Cancer Patients.

Microsatellite instability (MSI), high tumor mutation burden (TMB-H) and programmed cell death 1 ligand 1 (PD-L1) expression are hot biomarkers related to the improvement of immunotherapy response. Two cohorts of non-small-cell lung cancer (NSCLC) were collected and sequenced via targeted next-generation sequencing. Drug analysis was then performed on the shared genes using three different databases: Drugbank, DEPO and DRUGSURV. A total of 27 common genes were mutated in at least two groups of TMB-H-, MSI- and PD-L1-positive groups. AKT1, SMAD4, SCRIB and AXIN2 were severally involved in PI3K-activated, transforming growth factor beta (TGF-ß)-activated, Hippo-repressed and Wnt-repressed pathways. This study provides an understanding of the mutated genes related to the immunotherapy biomarkers of NSCLC.

Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.

The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.

Pathological complete response to neoadjuvant ceritinib of a crizotinib-resistant, stage IIIB non-small cell lung cancer with ALK rearrangement: A case report.

The treatment of stage IIIB non-small cell lung cancer (NSCLC) is complicated, the best strategy is chosen individually and surgery is usually not recommended. A 50-year-old female was diagnosed with locally advanced lung adenocarcinoma (stage IIIB, T2bN3M0). Fluorescence in situ hybridization (FISH) analysis revealed an ALK rearrangement. Crizotinib was administered and progression was seen after five months. The patient then received ceritinib with a palliative intent, which led to downstaging (IIIA[N2]) with a radiological and metabolic response. Right lower lobe lobectomy was performed at 12 months post-surgery, and the patient is still disease-free according to the last computed tomography (CT) scan. The unintended downstaging from ceritinib provided a chance for resection in our patient who had ALK-positive stage IIIB NSCLC after the failure of first-line crizotinib, indicating potential usage of ceritinib in the neoadjuvant setting. Future perspective trials are warranted to investigate the role of ceritinib in earlier stages as a primary drug.

Characteristics of T-Cell Receptor Repertoire and Correlation With EGFR Mutations in All Stages of Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T-cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. To comprehensively profile the TCR repertoire, results from high-throughput sequencing of samples from 93 Chinese patients with lung cancer were analyzed. We found that the TCR clonality of tissues was related to smoking, with higher clonality in patients who had quit smoking for less than 1 year. As expected, TCR clonality was correlated with stages: patients with stage IV disease showed higher clonality than others. The correlation between TCR repertoire and epidermal growth factor receptor (EGFR) status was also investigated. Patients with EGFR non-L858R mutations showed higher clonality and a lower Shannon index than other groups, including patients with EGFR L858R mutation and wild-type EGFR. Furthermore, we analyzed the TCR similarity metrics-that is, the TCR shared between postoperative peripheral blood and tissue of patients with non-distant metastasis of lung cancer. A similar trend was found, in which patients with EGFR L858R mutations had lower overlap index (OLI) and Morisita index (MOI) scores. Moreover, the OLI showed a positive correlation with several clinical characteristics, including the tumor mutational burden of tissues and the maximum somatic allele frequency of blood; OLI showed a negative correlation with the ratio of CD4+CD28+ in CD4+ cells and the ratio of CD8+CD28+ in CD8+ cells. In conclusion, TCR clonality and TCR similarity metrics correlated with clinical characteristics of patients with lung cancer. Differences in TCR clonality, Shannon index, and OLI across EGFR subtypes provide information to improve understanding about varied responses to immunotherapy in patients with different EGFR mutations.

Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report.

Tumour lysis syndrome (TLS) represents a group of fatal metabolic derangements resulting from the rapid breakdown of tumour cells. TLS typically occurs soon after the administration of chemotherapy in haematologic malignancies but is rarely observed in solid tumours. Here, we report a case of brigatinib-induced TLS after treatment with sequential anaplastic lymphoma kinase (ALK) inhibitors in a patient with advanced ALK-rearranged lung adenocarcinoma. The patient was treated sequentially with crizotinib, alectinib, and ensartinib. High-throughput molecular profiling after disease progression indicated that brigatinib may overcome ALK resistance mutations, so the patient was administered brigatinib as the fourth-line treatment. After 22 days of therapy, he developed oliguria, fever, and progressive dyspnoea. Clinical manifestations and laboratory findings met the diagnostic criteria for TLS. The significant decrease in the abundance of ALK mutations in plasma indicated a therapeutic response at the molecular level. Consequently, the diagnosis of brigatinib-induced TLS was established. To the best of our knowledge, this is the first case of TLS induced by sequential targeted therapy in non-small cell lung cancer. With the extensive application of sequential therapy with more potent next-generation targeted therapeutic drugs, special attention should be given to this rare but severe complication.

Survival and prognostic factors of lung cancer patients with preexisting connective tissue disease: a retrospective cohort study.

BACKGROUND: Connective tissue diseases (CTDs) are a group of special commodities in lung cancer (LC). This study aimed to analyze the survival and prognostic factors of LC patients with preexisting CTDs. METHODS: A total of 84 LC patients with preexisting CTDs that presented at Peking Union Medical College Hospital (PUMCH) were retrospectively recruited in this study between January 2000 and June 2017. Patient survival was compared using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to assess prognostic variables. RESULTS: Of the 84 LC patients, 36 (41.8%) had underlying rheumatoid arthritis (RA), 20 (23.8%) had idiopathic inflammatory myopathy (IIM), 18 (21.4%) had Sjögren syndrome (SS), 6 (7.1%) had systemic sclerosis (SSc), and 4 (4.8%) had systemic lupus erythematosus (SLE). The median overall survival (OS) was 21 months (IQR, 8-72 months), and the 1-, 3-, and 5-year survival rates were 61.3%, 36.7%, and 29.5%, respectively. The survival rates between different CTD subgroups, histopathologies, and disease stages were significantly different (P<0.05). Multivariate analysis showed that the independent prognostic factors for OS were IIM [hazard ratio (HR), 3.61; 95% confidence intervals (CI), 1.69-8.21; P=0.002], SS (HR, 2.72; 95% CI, 1.01-7.33; P=0.048), and radical resection (HR, 0.11; 95% CI, 0.04-0.35; P<0.001). CONCLUSIONS: Different CTD subtypes and the radical resection of LC are closely related to patient prognosis. This indicates a need for both identifications of CTD types and active treatment strategies for LC.

Neoadjuvant immunotherapy plus chemotherapy achieved pathologic complete response in stage IIIB lung adenocarcinoma harbored EGFR G779F: a case report.

The majority of patients with lung cancer are in the late stage (stages IIIB or IV) when diagnosed. However, clinical features, treatment and prognosis of some patients in stage IIIB are somewhat different from those in stage IV. Several clinical trials of neoadjuvant immunotherapy are changing the treatment strategy for patients with stage IB-IIIA non-small cell lung cancer (NSCLC). It remains unclear whether patients with stage IIIB NSCLC could benefit from neoadjuvant immunotherapy because they are often excluded from clinical trials. The IMpower150 trial showed promising results in the clinics of atezolizumab plus bevacizumab plus chemotherapy in patients with epidermal growth factor receptor (EGFR) mutation positive NSCLC. However, reports of this treatment strategy on EGFR exon 20 mutations are still lacking. Osimertinib is effective for T790M mutation but results of targeted therapy in other EGFR exon 20 mutations are not favorable and there is currently no effective long-term therapy. Patients harboring EGFR exon 20 G779F mutation have not been reported to achieve a complete response (CR). Here, we report the case of a 55-year-old man who was diagnosed as stage IIIB (cT1bN3M0) pulmonary adenocarcinoma by supraclavicular lymph node biopsy. He was administered chemotherapy plus durvalumab before surgery. The disease was considered as a partial response (PR), and the postoperative pathology revealed that a pathologic CR had been achieved. At the time of writing, no signs of recurrence had been observed in the preceding 15 months. Our case provides a new treatment option for such patients.

Circular RNA circMAGI3 accelerates the glycolysis of non-small cell lung cancer through miR-515-5p/HDGF.

The emerging roles of circular RNAs (circRNAs) in non-small cell lung cancer (NSCLC) have been convincingly proved. However, there are still numerous unknown circRNAs needing exploration. Here, present research performed a circRNA microarray analysis for the expression profile and identified a novel circRNA (circMAGI3, hsa_circ_0110498). Clinically, circMAGI3 was significantly up-regulated in NSCLC tissue and cells, which was closely correlated with unfavorable outcome for NSCLC patients. Functionally, circMAGI3 promoted the glycolysis and proliferation of NSCLC cells. Mechanistically, circMAGI3 functioned as a sponge for miR-515-5p to relieve its target gene HDGF expression, thereby accelerating the glycolysis of NSCLC. Collectively, this research identified the oncogenic role of circMAGI3 in the tumorigenesis through miR-515-5p/HDGF axis, providing a vital theoretical basis for treatment of NSCLC.

Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q.

Epidermal growth factor receptor (EGFR) L718Q is a rare resistant mutation which independently leads to third-generation tyrosine kinase inhibitor (TKI) resistance. Although a few studies have examined its resistance mechanisms, no effective treatment strategy has yet been proposed for patients with this mutation. Here, we report an effective treatment strategy for the rare EGFR L718Q mutation for the first time. A 44-year-old Chinese male patient initially presented with the sensitizing EGFR L858R mutation, and the progression-free survival (PFS) time after initial icotinib treatment was 9 months. When the progression of the disease (PD) and the EGFR T790M mutation were identified, he did not respond to the osimertinib treatment. Through comprehensive next-generation sequencing (NGS) of the surgical specimen, the rare EGFR L718Q mutation was eventually identified as having a frequency of 68.84%, together with an EGFR amplification with a copy number of 11.54. The previous treatment response was retrospectively explained, and the patient faced the challenge of not being able to benefit from any targeted therapy. Following chemotherapy with a personalized regimen which effectively modified the proportion of sensitive and resistant cells, significant response to osimertinib re-challenge was observed, and another PFS of 4.7 months was achieved. Unfortunately, four EGFR mutations, EGFR L858, T790M, L718Q, and C797S, were simultaneously detected in his late stage, and led to further progression of disease.

Over-expression of miR-145-5p inhibits malignant biological behaviors of esophageal squamous cells carcinoma via down-regulating IGF1R / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the mechanism of miR-145-5p on malignant biological behaviors, such as pro-liferation, invasion, migration and epithelial-mesenchymal transition (EMT), of esophageal squamous cell carcinoma (ESCC) TE-10 cells. Methods: The expression of miR-145-5p in ESCC cell lines and normal cells was detected by PCR. Dual luciferase reporter gene assay was used to detect the targeted regulation between miR-145-5p and insulin-like growth factor 1 receptor (IGF1R). The expres-sions of IGF1R protein and EMT related proteins were detected by Western blotting. Transwell assay and CCK-8 assay were carried out to detect the effects of miR-145-5p/IGF1R axis on the proliferation, migration andinvasionofTE-10 cells. Results: miR-145-5p was down-regulated in ESCC cell lines with the lowest expression in TE-10 cells (P<0.01orP<0.05).Over-expression of miR-145-5p significantly inhibited proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Dual luciferase reporter gene assay con-firmed that miR-145-5p targetedly down-regulated IGF1R expression (P<0.01). The restora-tion experiments further confirmed that simultaneous over-expression of miR-145-5p and IGF1R significantly attenuated the promotion effect of IGF1R on proliferation, invasion, migration and EMT of TE-10 cells (P<0.01 or P<0.05). Conclusions: Over-expression of miR-145-5p inhibits proliferation, invasion, migration and EMT of ESCC TE-10 cells by down-regulating IGF1R.

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib.

BACKGROUND: ALK-rearranged non-small cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC. However, heterogeneity of clinical responses exists among different ALK fusion partners. Several small studies have investigated the correlation between fusion partners and efficacy, but not yielded consistent results. OBJECTIVE: We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants. PATIENTS AND METHODS: We retrospectively reviewed genomic profiling and clinical data of 110 ALK-rearranged NSCLC patients from five centers. The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed. RESULTS: A total of 134 ALK rearrangements with 39 partners were identified in 110 patients (5.6%) among a cohort of 1971 NSCLC patients. The most frequently occurring ALK fusion partner was EML4, which was identified in 71.6% (96/134) of all of the rearrangements in 87.3% (96/110) patients, and with variant 3 (41/96, 42.7%) as the main variant type. No statistically significant differences in terms of progression-free survival (PFS) and overall survival (OS) were found between EML4-ALK and non-EML4-ALK NSCLC patients in our cohort (PFS, p = 0.207; OS, p = 0.678). Outcomes did not differ significantly between patients above and below 40 years of age (PFS, p = 0.427; OS, p = 0.686), nor between patients treated with crizotinib in different lines of therapy (PFS, p = 0.171; OS, p = 0.922). For EML4-ALK-positive NSCLC (n = 96), patients harboring variant 3 or variant 5 displayed significantly lower PFS and OS than those with other variants (PFS, 8.6 vs. 11.3 months, p = 0.046; OS, 31.0 vs. 37.6 months, p = 0.026). In addition, patients with a single EML4-ALK rearrangement event displayed favorable PFS (10.0 vs. 7.2 months, p = 0.040) and OS (36.0 vs. 20.0 months, p = 0.029) compared to those harboring multiple ALK rearrangements. CONCLUSIONS: This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.

Efficacy of on-pump coronary artery bypass grafting and stent implantation combined with surgery on lung cancer.

PURPOSE: Diaphragmatic hernia following an esophagectomy for esophageal cancer (EC) can be both an early and late complication. The esophageal hiatus within the diaphragm is disrupted during the operation. However, the incidence of Post-Esophagectomy Diaphragmatic Hernia (PEDH) is unknown. PEDH can be life-threatening and surgical treatment is challenging. However, all PEDH do not require surgery. The rate of EC diagnosis is rising. Therefore, esophageal surgery, particularly esophagectomy, is gradually increasing. Undoubtedly, the numbers of PEDH increase as well. METHODS: This review describes the presentation and diagnosis of PEDH after surgery for esophageal malignancy, as well as the management options for PEDH. RESULTS: Fifteen papers regarding PEDH have been published. There are many different surgical approaches to complete an esophagectomy, while there are different approaches to repair PEDH. CONCLUSION: Upper GI surgeons need to have an index of suspicion for PEDH. They must investigate and operate these patients if this complication develops, since an immediate surgery has a high mortality and poor outcome.

The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway.

The action mechanism of long non-coding ribonucleic acid-homeobox transcript antisense ribonucleic acid (lncRNA-HOTAIR) in the regulation of the Wnt signaling pathway on the drug resistance of non-small cell lung cancer was investigated. Forty eight patients with non-small cell lung cancer, who were treated with cisplatin (DDP) as neoadjuvant chemotherapy, were selected from the specimen bank of the Department of Pathology of Peking Union Medical College Hospital. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger RNA (mRNA) level of lncRNA-HOTAIR in cancer and cancer-adjacent tissues. The correlation curve of the expression of lncRNA-HOTAIR with the overall survival (OS) was plotted using the Kaplan-Meier method. NCI-H1299 DDP-resistant cell lines were constructed, and the half maximal inhibitory concentration (IC50) value was measured. The expression of lnc-HOTAIR in NCI-H1299/DDP cells was detected by the target interference of small interfering RNA (siRNA). The effect of si-HOTAIR on cell resistance was detected by Cell Counting Kit-8 (CCK-8). Western blot analysis was used to detect the effects of si-HOTAIR on multidrug resistance proteins, multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 1 (MDR1), and Wnt signaling pathways, Wnt3a, adenomatous polyposis coli (APC) and ß-catenin. The mRNA level of lncRNA-HOTAIR in cancer tissues was significantly higher than that in cancer-adjacent tissues (P<0.05), and the high expression of lncRNA-HOTAIR indicated that the OS of patients was shortened (P<0.05). The IC50 of NCI-H1299/DDP cells inhibiting DDP was 127.82 µM, which was significantly higher than that of parental NCI-H1299 cells (IC50=8.40 µM) (P<0.05). si-HOTAIR interference significantly decreased the sensitivity of cells to DDP, the IC50 of cells was decreased from 131.85 to 44.34 µM (P<0.05), the expression levels of MRP1 and MDR1 were significantly decreased, and the activation of Wnt signaling pathway was significantly inhibited (P<0.05). Thus, lncRNA-HOTAIR plays an important role in the occurrence and development of non-small cell lung cancer, and it may be an important factor in the clinical prognosis of patients with non-small cell lung cancer.

[ARTICLE WITHDRAWN] MicroRNA-539 Inhibits the Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Twist-Related Protein 1-Mediated Modulation of Melanoma-Associated Antigen A4.

This article has been withdrawn at the request of the publisher in December 2020.