Prediction and verification of benignancy and malignancy of pulmonary nodules based on inflammatory related biological markers.

Objective: Inflammation plays an important role in the transformation of pulmonary nodules (PNs) from benign to malignant. Prediction of benignancy and malignancy of PNs is still lacking efficacy methods. Although Mayo or Brock model have been widely applied in clinical practices, their application conditions are limited. This study aims to construct a diagnostic model of PNs by machine learning using inflammation-related biological markers (IRBMs). Methods: Inflammatory related genes (IRGs) were first extracted from GSE135304 chip data. Then, differentially expressed genes (DEGs) and infiltrating immune cells were screened between malignant pulmonary nodules (MN) and benign pulmonary nodule (BN). Correlation analysis was performed on DEGs and infiltrating immune cells. Molecular modules of IRGs were identified through Consistency cluster analysis. Subsequently, IRBMs in IRGs modules were filtered through Weighted gene co-expression network analysis (WGCNA). An optimal diagnostic model was established using machine learning methods. Finally, external dataset GSE108375 was used to verify this result. Results: 4 hub IRGs and 3 immune cells showed significantly difference between MN and BN, C1 and C2 module, namely PRTN3, ELANE, NFKB1 and CTLA4, T cells CD4 naïve, NK cells activated and Monocytes. IRBMs were screened from black module and yellowgreen module through WGCNA analysis. The Support vector machines (SVM) was identified as the optimal model with the Area Under Curve (AUC) was 0.753. A nomogram was established based on 5 hub IRBMs, namely HS.137078, KLC3, C13ORF15, STOM and KCTD13. Finally, external dataset GSE108375 verified this result, with the AUC was 0.718. Conclusion: SVM model established by 5 hub IRBMs was able to effectively identify MN or BN. Accumulating inflammation and immune dysfunction were important to the transformation from BN to MN.

Guidelines for the clinical application of the Xihuang pill for the prevention and treatment of breast hyperplasia diseases.

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Vitamin E intake is inversely associated with NAFLD measured by liver ultrasound transient elastography.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, whose severe form is associated with oxidative stress. Vitamin E as an antioxidant has a protective potential in NAFLD. Whether dietary intake of vitamin E, supplementary vitamin E use, and total vitamin E have a preventive effect on NAFLD requires investigation. A cross-sectional study used data from the National Health and Nutrition Examination Survey (2017-2020) was conducted. Vitamin E intake, including dietary vitamin E, supplementary vitamin E use, and total vitamin E, was obtained from the average of two 24-h dietary recall interviews. The extent of hepatic steatosis was measured by liver ultrasound transient elastography and presented as controlled attenuated parameter (CAP) scores. Participants were diagnosed with NAFLD based on CAP threshold values of 288 dB/m and 263 dB/m. The statistical software R and survey-weighted statistical models were used to examine the association between vitamin E intake and hepatic steatosis and NAFLD. Overall, 6122 participants were included for NAFLD analysis. After adjusting for age, gender, race, poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, abdominal circumference, hyperlipidemia, hypertension, diabetes, and supplementary vitamin E use, dietary vitamin E was inversely associated with NAFLD. The corresponding odds ratios (OR) and 95% confidence intervals (CI) of NAFLD for dietary vitamin E intake as continuous and the highest quartile were 0.9592 (0.9340-0.9851, P = 0.0039) and 0.5983 (0.4136-0.8654, P = 0.0091) (Ptrend = 0.0056). Supplementary vitamin E was significantly inversely associated with NAFLD (fully adjusted model: OR = 0.6565 95% CI 0.4569-0.9432, P = 0.0249). A marginal improvement in total vitamin E for NAFLD was identified. The ORs (95% CIs, P) for the total vitamin E intake as continuous and the highest quartile in the fully adjusted model were 0.9669 (0.9471-0.9871, P = 0.0029) and 0.6743 (0.4515-1.0071, P = 0.0538). Sensitivity analysis indicated these findings were robust. The protective effects of vitamin E significantly differed in the stratum of hyperlipidemia (Pinteraction < 0.05). However, no statistically significant results were identified when the threshold value was set as 263 dB/m. Vitamin E intake, encompassing both dietary and supplemental forms, as well as total vitamin E intake, demonstrated a protective association with NAFLD. Augmenting dietary intake of vitamin E proves advantageous in the prevention of NAFLD, particularly among individuals devoid of hyperlipidemia.

Chinese and Western Integrative Medicine for Stage IIIb-IVb Non-Small Cell Lung Cancer: Design and Rationale of a Multi-center, Prospective Registry (NSCLC-Chinese and Western Integrative Medicine cohort).

INTRODUCTION: This planned multicenter observational study will evaluate the overall survival of those undergoing integrated Chinese and Western medicine for stage IIIb-IVb non-small cell lung cancer and analyze the factors related to the prognosis. METHOD AND ANALYSIS: The prospective cohort will enroll patients with stage IIIb-IVb NSCLC from March 1, 2019, to December 31, 2025, and follow them for 5 years. We plan to collect data on the patients' demographics, treatment, overall survival, and factors related to the prognosis. ETHICS AND DISSEMINATION: The institutional review board and ethics committee reviewed the study protocol. All patients will provide informed consent before enrollment.Trial registration number: ChiCTR1900021430.

Effect of Fu's subcutaneous needling for cancer pain management: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Pain is a common symptom in patients with cancer, and pain management is crucial for these patients. Fu's subcutaneous needling (FSN) is a modern acupuncture therapy based on basic medicine commonly used in patients with pain. However, evidence of its effectiveness in treating cancer pain has not been systematically proven. Therefore, this pragmatic randomised controlled trial aims to evaluate the effectiveness and safety of FSN for cancer pain management. METHODS AND ANALYSIS: Overall, 120 eligible patients will be recruited and randomly assigned into two groups using block randomisation. Both groups will be administered analgesic drugs according to the National Comprehensive Cancer Network guidelines. The treatment group will receive FSN therapy one time a day for 6 days. Additionally, we will assess analgesic consumption as the primary outcome and the Numerical Rating Scale, outbreak pain, symptom assessment and adverse events as secondary outcomes to evaluate the effect and safety of FSN in treating cancer pain. The incidence of adverse events will be monitored to assess the safety of FSN. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (approval No: K(2021)096). The results will be published in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls. TRIAL REGISTRATION NUMBER: ChiCTR2200056348.

Case Report: Clinical benefit from multi-target tyrosine kinase inhibitor and PARP inhibitor in a patient with cancer of unknown primary with BRCA1 large genomic rearrangement.

Background: Cancer of unknown primary (CUP), which accounts for 3%-5% of new cancer cases every year, involves the presence of a type of histologically confirmed metastatic tumors whose primary site cannot be confirmed by conventional diagnostic methods. This difficulty in identifying the primary site means that CUP patients fail to receive precisely targeted therapy. Most patients are treated with empiric chemotherapy, with a median survival of 6 months and even poorer prognosis within an unfavorable subset of CUP. Case report: An 80-year-old woman presented with masses in the abdomen. Following comprehensive imagological and immunohistochemical examinations, she was diagnosed with CUP. She emphatically declined chemotherapy; thus, anlotinib has been administered with patient consent since 02/07/2019, and stable disease (SD) was observed for 2 years. During subsequent treatment, a large genomic rearrangement in BRCA1 was identified in the patient via NGS, and SD was observed for a further 6 months following olaparib treatment. The type of LGR identified in this patient was discovered to be BRCA1 exon 17-18 inversion (inv), which has never been previously reported. Conclusion: For CUP patients, a chemo-free regimen seems to be acceptable as a first-line treatment, and NGS-guided targeted treatment could improve patient outcomes.

Yifei Sanjie Formula or Placebo With Anlotinib as Second-Line or Above Treatment for Metastatic Non-Small-Cell Lung Cancer: Study Protocol for a Double-Blind, Placebo-Controlled Randomized Pilot Study.

BACKGROUND: Anlotinib is used as a third-line treatment for advanced non-small-cell lung cancer (NSCLC), but has limited clinical benefits and several side effects, such as diarrhea and acneiform skin rash. Traditional Chinese Medicine (TCM) is commonly used to treat cancers in China. Chinese herbal medicines may have the potential as adjuvant therapies to reduce toxicity and improve the efficacy of treatments for NSCLC. Given the positive outcomes of basic research, we plan to evaluate whether the addition of the Chinese herbal medicine Yifei Sanjie formula (YFSJF) to anlotinib can improve the progression-free survival (PFS) of advanced NSCLC patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled parallel-group controlled pilot trial will be performed. Forty eligible patients will be randomized in a ratio of 1:1 to the intervention (YFSJF + anlotinib) and control (placebo + anlotinib) groups. Participants will be advised to take 12 mg/day of anlotinib on days 1 to 14 of each 21-day cycle. YFSJF or placebo will be administered (15 g twice daily) during each cycle until progression of disease (PD). The primary outcome will be progression-free survival (PFS), and the secondary outcomes will be overall survival (OS), the objective response rate (ORR), and patient-reported outcomes (PRO). Tumors will be assessed based on RECIST v. 1.1 after every 2 cycles of treatment. The M. D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to evaluate PRO at baseline and weekly thereafter until PD. DISCUSSION: This will be the first trial to evaluate the effectiveness and safety of TCM combined with anlotinib for the treatment of NSCLC. The results of this randomized controlled trial will fill a gap in the research by showing whether YFSJF combined with anlotinib can improve PFS in NSCLC patients. TRIAL REGISTRATION: The study was registered on June 8th, 2021 on Chinese Clinical Registry; registration number ChiCTR2100047143. (https://www.chictr.org.cn/index.aspx). ETHICS AND DISSEMINATION: The Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine approved the study protocol (approval no.: K2020151, 2021/08/19). The study will also be supervised and managed by the Ethics Committee.

Posterior reversible encephalopathy syndrome associated with use of anlotinib to treat squamous cell carcinoma of the cervix: case report and literature review.

Background: Posterior reversible encephalopathy syndrome (PRES), a neurological disorder with an unknown aetiology, is characterised by visual impairment, headache, vomiting, seizures, and transient alterations in consciousness. Case report: We present the case of a 49-year-old woman with advanced cervical carcinoma who received second-line therapy with oral anlotinib (12 mg, days 1-14, every 21 days) and injectable tislelizumab (200 mg, day 1, every 21 days). After 7 days of anlotinib administration, she began experiencing symptoms suggestive of PRES and was diagnosed on day 11. Interruption of anlotinib and supportive treatment led to recovery of her binocular vision. The Naranjo score (+5) graded the causality of this reaction as probable, suggesting the possibility that the event may have been an adverse reaction to anlotinib. Ethics: This case report was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Reference no. K-2023-068, 2023/06/09). Informed consent was obtained from the patient and her family.

Qu-Yu-Jie-Du Decoction Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulation of Neutrophils and Macrophage Infiltration.

Background: Inflammatory bowel disease (IBD) is becoming a global disease. A percentage of IBD patients will not react to therapy or will lose their response. Qu-Yu-Jie-Du Decoction (QYJD) is a traditional Chinese medicine formula commonly used for intestinal diseases. It has been reported that QYJD has an anti-inflammatory effect, but the mechanism is not fully understood. In this study, we mainly evaluated the anti-inflammatory effect of QYJD and explored the possible mechanisms. Methods: Twenty-four BALB/c mice were randomly divided into 4 groups according to their body weight, namely, the control group, the dextran sulfate sodium (DSS) group, the DSS + QYJD group, and the QYJD group. Mice were given 3% DSS drinking water freely, and at the same time, mice were given normal saline or QYJD (4.44 mg/g/d), respectively. Mental state, faeces, and weight were recorded every day. On the 10th day, the mice were sacrificed and collected for investigation. The length of the mice colon was measured. Histological analysis was used to detect the morphological changes in the colon. Immunohistochemistry was used to measure the infiltration of macrophages (F4/80, CD163) and neutrophils (Ly6G). Colorimetry was used to detect the myeloperoxidase (MPO) activity of colon tissues. ELISA was utilized to detect associated inflammatory cytokines and chemokines in colon tissues. Results: QYJD alleviated the weight loss and colitis symptoms of mice caused by DSS. QYJD fought against the shortening of the intestine caused by DSS; that is, it improved the decline of intestinal compliance in mice and had a protective effect on colon tissues. The mechanisms were related to downregulating macrophages and neutrophils in colon tissues of infiltration. Besides, QYJD simultaneously reduced the activity of myeloperoxidase activity (MPO) and the contents of IL-1ß, IL-6, TNF-α, TGF-ß, CCL2, and CXCL2 in colon tissues. Conclusions: QYJD can ameliorate DSS-induced colitis in mice and the mechanism is connected with a reduction in neutrophil and macrophage infiltration.

Zhengyuan capsules for the treatment of chemotherapy-induced cancer-related fatigue in stage IIIB-IV unresectable NSCLC: study protocol for a randomized, multi-center, double-blind, placebo-controlled clinical trial.

Background: Patients with advanced non-small cell lung cancer (NSCLC) frequently experience cancer-related fatigue (CRF) during or after chemotherapy. Traditional Chinese medicine (TCM) can effectively relieve CRF, although the clinical evidence is insufficient due to the absence of extensive and rigorous clinical studies. Zhengyuan capsules have both tonifying and dispersing effects, and its ability to alleviate CRF has been verified in mice. This study aimed to provide evidence for the role of proprietary Chinese medicines in alleviating CRF in advanced NSCLC patients. Methods: A multi-center, randomized, double-blind, placebo-controlled clinical trial has been designed to evaluate the efficacy and safety of Zhengyuan capsules for CRF in stage IIIB-IV unresectable NSCLC patients undergoing chemotherapy. Thirty eligible participants will be randomized into two groups at a 1:1 ratio during chemotherapy using the centralized interactive web response system. All patients will receive conventional platinum-based dual-drug chemotherapy and Zhengyuan capsules or simulant for 42 consecutive days starting on the first day of the first week of chemotherapy. The primary outcome is the difference between baseline and post-treatment CRF in the two groups, which will be assessed using the Brief Fatigue Inventory (BFI) score. Secondary outcome measurements include the Revised Piper's Fatigue Scale (RPFS)-Chinese Version, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Module C30 (EORTC QLQ-C30) v3.0 combined with EORTC QLQ-LC13 (Lung Cancer 13), clinical symptom score, hematology exploratory index, and progression-free survival. And safety indicators such as blood, urine, fecal routine, liver and kidney function, coagulation, and electrocardiogram will be performed before chemotherapy. Data will be analyzed according to intention-to-treat (ITT) and per-protocol (PP) principles; Empowerstats and R will be applied for statistical analysis. Discussion: This trial will provide data on the efficacy and safety of Zhengyuan capsules for treating CRF in stage IIIB-IV unresectable NSCLC patients undergoing chemotherapy. It will also provide a basis for the feasibility of a large-scale clinical trial. Trial Registration: The clinical trial was registered on 19 November 2020 through https://www.chictr.org.cn (registration number: ChiCTR2000040061).

Efficacy of Disitamab Vedotin in a heavily pre-treated HER2 positive lung adenocarcinoma patient: case report and literature review.

Cancer therapies targeting human epidermal growth factor receptor 2 (HER2) have been attracting increasing attention worldwide, especially in lung adenocarcinoma. Disitamab vedotin is an antibody-drug conjugate designed for targeting HER2 that has been approved for urothelial carcinoma and gastric cancer. However, there is still a lack of clinical evidence for applying Disitamab vedotin in lung adenocarcinoma. Herein, we reported a case of a 52-year-old man with advanced lung adenocarcinoma carrying HER2 amplification as well as HER2 immunohistochemistry (IHC) 2 + who underwent treatment with Disitamab vedotin after disease progression. The patient was treated with chemotherapy, anti-angiogenesis therapy, and immunotherapy as first-line therapy, achieving a remarkable progression-free survival of 16 months. After the disease continued to continuous progress, the patient was administrated with Disitamab vedotin, which resulted in improvement of both the lung lesions and the brain lesions. Our findings provide a valuable reference for the utilization of Disitamab Vedotin in HER2 IHC2+ lung adenocarcinoma.

The Prognostic Value of Serum Apolipoprotein A-I Level and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Liver Metastasis.

Background: Colorectal cancer liver metastasis (CRLM) is a high degree of malignancy with rapid disease progression and has a poor prognosis. Both serum apolipoprotein A-I (ApoA-I) and neutrophil-to-lymphocyte ratio (NLR) play key roles in anti-inflammation and antitumor. This study is aimed at evaluating the implication of serum ApoA-I level in combination with NLR in the prognosis of CRLM. Methods: We retrospectively analyzed the serum ApoA-I level and NLR in 237 patients with CRLM. Cox regression analyses were used to identify the independent prognostic significance of these indicators. Kaplan-Meier method and Log-rank test were applied to compute overall survival (OS). Both the ApoA-I and NLR were divided into three levels, according to their medians. A risk-stratified prediction model was established to evaluate the prognosis of patients with CRLM. The ROC curve AUC values were applied to evaluate the capability of the model. Results: Higher levels of ApoA-I and lower NLR were strongly associated with prolonged OS (Log-rank test, P < 0.05). The patients were then grouped into three queues according to the ApoA-I level and NLR. There was a crucial diversity in the OS (P < 0.001) between the high-risk (ApoA - I ≤ 1.03 g/L and NLR > 3.24), medium-risk (ApoA - I > 1.03 g/L or NLR ≤ 3.24) and low-risk groups (ApoA - I > 1.03 g/L and NLR ≤ 3.24). The AUC value of the prediction model (AUC = 0.623, 95% CI: 0.557-0.639, P = 0.001) was higher than other individual indicators (including ApoA-I, NLR, cT classification, and cN classification). Additionally, the association of the prediction model and cTN classification (AUC = 0.715, 95% CI: 0.606-0.708, P < 0.001) was better than the model and cTN classification alone. Conclusion: The combination of ApoA-I level and NLR could be a prognostic indicator for CRLM.

Lung adenocarcinoma with an uncommon CCDC85A-ALK fusion responding to alectinib: A case report.

A 55-year-old Chinese man with a right lung mass and lymph node metastasis (T4N3M0 IIIB) was diagnosed with lung adenocarcinoma after a CT-guided biopsy. With the wide application of next-generation sequencing (NGS) in tumour detection, we found a rare CCDC85A-ALK fusion. The patient received alectinib, which had marked efficacy. This is the first report of a lung adenocarcinoma patient harbouring a new uncommon anaplastic lymphocyte kinase fusion that showed a remarkable response to alectinib. NGS aids in selecting treatment in non-small cell lung cancer patients.

Comprehensive analysis of an immune infiltrate-related competitive endogenous RNA network reveals potential prognostic biomarkers for non-small cell lung cancer.

Globally, non-small cell lung cancer (NSCLC) is the most common malignancy and its prognosis remains poor because of the lack of reliable early diagnostic biomarkers. The competitive endogenous RNA (ceRNA) network plays an important role in the tumorigenesis and prognosis of NSCLC. Tumor immune microenvironment (TIME) is valuable for predicting the response to immunotherapy and determining the prognosis of NSCLC patients. To understand the TIME-related ceRNA network, the RNA profiling datasets from the Genotype-Tissue Expression and The Cancer Genome Atlas databases were analyzed to identify the mRNAs, microRNAs, and lncRNAs associated with the differentially expressed genes. Weighted gene co-expression network analysis revealed that the brown module of mRNAs and the turquoise module of lncRNAs were the most important. Interactions among microRNAs, lncRNAs, and mRNAs were prognosticated using miRcode, miRDB, TargetScan, miRTarBase, and starBase databases. A prognostic model consisting of 13 mRNAs was established using univariate and multivariate Cox regression analyses and validated by the receiver operating characteristic (ROC) curve. The 22 immune infiltrating cell types were analyzed using the CIBERSORT algorithm, and results showed that the high-risk score of this model was related to poor prognosis and an immunosuppressive TIME. A lncRNA-miRNA-mRNA ceRNA network that included 69 differentially expressed lncRNAs (DElncRNAs) was constructed based on the five mRNAs obtained from the prognostic model. ROC survival analysis further showed that the seven DElncRNAs had a substantial prognostic value for the overall survival (OS) in NSCLC patients; the area under the curve was 0.65. In addition, the high-risk group showed drug resistance to several chemotherapeutic and targeted drugs including cisplatin, paclitaxel, docetaxel, gemcitabine, and gefitinib. The differential expression of five mRNAs and seven lncRNAs in the ceRNA network was supported by the results of the HPA database and RT-qPCR analyses. This comprehensive analysis of a ceRNA network identified a set of biomarkers for prognosis and TIME prediction in NSCLC.

A Three-Dimensional Co-Culture Model for Rheumatoid Arthritis Pannus Tissue.

Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.

Construction of a Novel Lung Adenocarcinoma Immune-Related lncRNA Pair Signature.

BACKGROUND: A growing number of studies have demonstrated that immune-related long noncoding ribonucleic acids (irlncRNAs) are potential prognostic factors for lung adenocarcinoma. Two-gene combination patterns could improve the sensitivity of prognostic models, providing us a novel signature construction concept that we applied to lung adenocarcinoma. METHODS: Gene expression and clinical data were downloaded from the Lung Adenocarcinoma project of The Cancer Genome Atlas (TCGA) database. We applied a co-expression analysis with immune genes obtained from the ImmPort database to recognize irlncRNA. The matrix of irlncRNA pairs was established by a cyclic comparison of each lncRNA pair expression level. Univariate and multivariate Cox regressions and Lasso penalized regression analysis were applied to construct the risk model. Patients with lung adenocarcinoma were divided into high- and low-risk groups, according to the Akaike Information Criterion (AIC) values of the receiver operating characteristic (ROC) curve. Then, we evaluated our signature under various clinical settings: clinical-pathological characteristics, tumor-infiltrating immune cells, checkpoint-related biomarkers, targeted therapy, and chemotherapy. RESULTS: Based on the 239 differently expressed irlncRNAs, we constructed an 11-irlncRNA pair signature. The area under the curve (AUC) of the ROC curve for the signature to predict the 4-year survival rate was 0.819, and the cut-off point was recognized as 1.003. Subsequent analysis showed that our signature can effectively distinguish unfavorable survival outcomes, prognostic clinic-pathological characteristics, and specify tumor infiltration status. Highly expressed immune checkpoint-related genes, as well as higher chemosensitivity, were correlated to the low-risk group. CONCLUSION: We constructed a novel lung adenocarcinoma irlncRNA signature with promising prognostic value using the TCGA database, based on paired irlncRNAs and not relying on lncRNAs special expression levels.

Comprehensive TCM treatments combined with chemotherapy for advanced non-small cell lung cancer: A randomized, controlled trial.

OBJECTIVE: We conducted this study to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in advanced non-small cell lung cancer (NSCLC) patients who underwent chemotherapy. DESIGN: This was a prospective, open-label, randomized controlled trial. NSCLC patients at stage IIIA, IIIB, or IV were randomly assigned to either TCM plus chemotherapy or chemotherapy alone. The comprehensive TCM treatment consisted of Kang Ai injection, herbal decoction, and Zhenqifuzheng capsules. The primary endpoint was quality of life (QOL) measured by the Functional Assessment of Cancer Therapy-Lung version 4.0. The secondary endpoints were chemotherapy completion rate, tumor response, and adverse events. All assessments were done at baseline, the third week, and the sixth week. RESULTS: Thirty-nine participants were randomly assigned to the treatment group and 36 to the control group. The QOL scores were significantly improved in the treatment group compared with those of the control group in social well-being (cycle 1, P = .048; cycle 2, P = .015), emotional well-being (cycle 1, P = .047; cycle 2, P = 4.29E-05), and functional well-being (cycle 1, P = .030; cycle 2, P = .003), while the QOL scores in the above 3 domains declined in the control group (P < .05). Both groups had a decline in the physical well-being score (cycle 1, P = .042; cycle 2, P = .017) and lung cancer symptom score (cycle 1, P = .001; cycle 2, P = .001) after 2 courses of intervention. The deterioration in physical well-being and lung cancer symptoms was noticeably smaller in the treatment group (P < .05). There were significant differences between the 2 groups in social well-being, emotional well-being, functional well-being, lung cancer symptom domain, and the total score (P < .05). Patients in the treatment group had a significantly lower incidence of platelet reduction than the control group (P = .028) after 2 cycles of treatment. No significant difference in nonhematological adverse events (AEs) was observed. CONCLUSION: This study illustrated that comprehensive TCM treatment could promote the QOL of NSCLC patients, alleviate symptoms, and reduce the AEs caused by chemotherapy, verifying the synergistic and attenuating effects of TCM in NSCLC patients undergoing chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR-TRC-13003637.

Metastatic Colorectal Cancer Patient With Microsatellite Stability and BRAFV600E Mutation Showed a Complete Metabolic Response to PD-1 Blockade and Bevacizumab: A Case Report.

A vast majority of colorectal cancer (CRC) patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) are refractory to immunotherapeutic strategies. The current research focusses on the combined treatment strategies for identification and optimization in order to improve the efficacy of immunotherapy among patients with microsatellite stability (MSS), who account for the majority of metastatic colorectal cancer (mCRC) cases. mCRC patients harboring MSS and the BRAFV600E mutation show a worse prognosis and barely benefit from immunotherapy. In this report, we discuss the case of a mCRC patient with MSS and BRAFV600E mutation, who exhibited significant response to the combined treatment with nivolumab and bevacizumab, and has been exhibiting a progression-free survival (PFS) of more than 17 months. Our findings indicate that combined anti-angiogenic therapy can improve the efficacy of immunotherapy, which results in the prolong survival of the patient. This is a case report on MSS and BRAFV600E colorectal cancer which presents with a response to immunotherapy and anti-angiogenic therapy.

Notch-1 and Notch-3 Mediate Hypoxia-Induced Activation of Synovial Fibroblasts in Rheumatoid Arthritis.

OBJECTIVE: To investigate the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch-1 and Notch-3 signaling, and to evaluate its potential as a therapeutic target. METHODS: Expression of Notch-1 intracellular domain (N1ICD), N3ICD, and hypoxia-inducible factor 1α (HIF-1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen-induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. RESULTS: N1ICD, N3ICD, and HIF-1α were expressed abundantly in the synovial tissue of RA patients. HIF-1α was shown to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia-induced N1ICD and N3ICD expression in RASFs was blocked by HIF-1α siRNA. Notch-1 siRNA and Notch-3 siRNA inhibited hypoxia-induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch-1 was shown to regulate RASF migration and epithelial-mesenchymal transition under hypoxic conditions, whereas Notch-3 was shown to regulate the processes of anti-apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. CONCLUSION: This study identified a functional link between HIF-1α, Notch-1, and Notch-3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.