Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients.

BACKGROUND: This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). METHODS: Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. RESULTS: Immunohistochemical staining showed that the tumors expressed CK7, S-100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. CONCLUSION: Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

Lycium barbarum glycopetide prolong lifespan and alleviate Parkinson's disease in Caenorhabditis elegans.

Introduction: Lycium barbarum glycopeptide (LbGp) is the main bioactive compound extracted from the traditional Chinese medicine. L. barbarum berries and has been proven to have numerous health benefits, including antioxidative, anti-inflammatory, anticancer, and cytoprotective activities. However, the antiaging effect of LbGp remains unknown. Methods: The lifespan and body movement of C. elegans were used to evaluate the effect of LbGp on lifespan and health span. The thrashing assay was used to determine the role of LbGp in Parkinson's disease. To investigate the mechanisms of LbGp-induced antiaging effects, we analyzed changes in lifespan, movement, and the expression of longevity-related genes in a series of worm mutants after LbGp treatment. Results: We found that LbGp treatment prolonged the lifespan and health span of C. elegans. Mechanistically, we found that LbGp could activate the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, as well as the nuclear receptor DAF-12, thereby upregulating longevity-related genes to achieve lifespan extension. In addition, we found that the lifespan extension induced by LbGp partially depends on mitochondrial function. Intriguingly, LbGp also ameliorated neurodegenerative diseases such as Parkinson's disease in a DAF-16-, SKN-1-, and HSF-1-dependent manner. Conclusion: Our work suggests that LbGp might be a viable candidate for the treatment and prevention of aging and age-related diseases.

[Updated Interpretation of the NCCN Clinical Practice Guidelines (Version 3. 2023) 
for Non-small Cell Lung Cancer].

Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China.
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Lipid metabolic characteristics and marker compounds of ripened Pu-erh tea during pile fermentation revealed by LC-MS-based lipidomics.

Ripened Pu-erh tea (RPT) is a unique microbial fermented tea. Herein, we investigated the lipid composition of RPT and its metabolic changes during pile fermentation, by nontargeted lipidomics profiling and quantitative analysis using liquid chromatography-mass spectrometry (LC-MS). A total of 485 individual lipid species covering 26 subclasses were detected, and fatty acid ester of hydroxy fatty acid (FAHFA) was detected in tea for the first time. Among them, 362 species were significantly altered during fermentation. Chlorophylls decomposition, phospholipids degradation (especially phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine), formation of free fatty acid (FFA) (especially FFA18:3, FFA18:2), and formation of FAHFA, were annotated as the key pathways. Particularly, FAHFAs were undetected in raw tea and gradually enriched to 227.0 ± 9.6 nmol/g after fermentation (p < 0.001), which could serve as marker compounds of RPT associated with microbial fermentation. This study will advance understanding the lipid metabolic fate in microbial fermentation and its role in RPT quality. Chemical compounds studied in this article: Linolenic acid (PubChem CID: 5280934); Linoleic acid (PubChem CID: 5280450); Oleic acid (PubChem CID: 445639); PS(22:0/18:2) (PubChem CID: 52925820); PS(20:0/18:3) (PubChem CID: 52925629); Pheophytin a (PubChem CID: 135398712); Pheophorbide a (PubChem CID: 253193).

Chemical profile of a novel ripened Pu-erh tea and its metabolic conversion during pile fermentation.

Ripened Pu-erh tea is a unique tea type produced from microbial fermentation. Recently, a novel ripened Pu-erh tea (NPT) produced using a patented pile fermentation method has become increasingly popular due to its improved flavor and enriched bioactive gallic acid (GA). However, the detailed chemical features of NPT and their formation during pile fermentation remain unclear. Herein, untargeted metabolomics revealed enrichment of GA, amino acids, free sugars and reduction in catechins and flavonol glycosides in NPT. Mainly, GA was 1.99 times higher in NPT than traditional Pu-erh tea (p < 0.001). The metabolic changes were tracked during pile fermentation, and possible pathways were mapped. GA enrichment may be produced from enhanced hydrolysis of galloyl catechins and phenolic acid esters. Degradation of flavonol glycosides and formation of other metabolites were observed. This study will advance our understanding of conversions during pile fermentation and provide new insights into directional manufacturing of high-quality ripened tea.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Investigation on green tea lipids and their metabolic variations during manufacturing by nontargeted lipidomics.

Lipids are hydrophobic metabolites implicated in tea flavor quality. Understanding their transformations during tea manufacture is of particular interest. To date, the detailed lipid composition and variations during green tea manufacture are largely unknown. Herein, we performed a comprehensive characterization of the dynamic changes of lipids during green tea manufacture, by applying nontargeted lipidomics using ultrahigh performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Exactive/MS) combined with chemometric tools. Totally, 283 lipid species were detected, covering 20 subclasses. Significant lipidomic variations were observed during green tea manufacture, especially in the fixation stage, mainly associated with chlorophyll decomposition, phosphatidic acids (PAs) reduction and glycolipids degradation, which potentially contribute to tea color and aroma quality. Specifically, the most prominent decrease of PAs content during green tea manufacture was identified for the first time. This study provides insights into the lipid metabolic fates upon green tea manufacture, and their roles in green tea sensory quality.

Rutin, γ-Aminobutyric Acid, Gallic Acid, and Caffeine Negatively Affect the Sweet-Mellow Taste of Congou Black Tea Infusions.

The sweet-mellow taste sensation is a unique and typical feature of premium congou black tea infusions. To explore the key taste-active compounds that influence the sweet-mellow taste, a sensory and molecular characterization was performed on thirty-three congou black tea infusions presenting different taste qualities, including the sweet-mellow, mellow-pure, or less-mellow taste. An integrated application of quantitative analysis of 48 taste-active compounds, taste contribution analysis, and further validation by taste supplementation experiments, combined with human sensory evaluation revealed that caffeine, γ-aminobutyric acid, rutin, succinic acid, citric acid, and gallic acid negatively affect the sweet-mellow taste, whereas glucose, sucrose, and ornithine positively contribute to the sweet-mellow taste of congou black tea infusions. Particularly, rutin, γ-aminobutyric acid, gallic acid, and caffeine, which impart the major inhibitory effect to the manifestation of the sweet-mellow taste, were identified as the key influencing components through stepwise screening and validation experiments. A modest level of these compounds was found to be favorable for the development and manifestation of the sweet-mellow taste. These compounds might potentially serve as the regulatory targets for oriented-manufacturing of high-quality sweet-mellow congou black tea.

Ginkgolic Acids Impair Mitochondrial Function by Decreasing Mitochondrial Biogenesis and Promoting FUNDC1-Dependent Mitophagy.

Ginkgolic acids (GAs) are found in the leaves, nuts, and testa of Ginkgo biloba and have been reported to exhibit antitumor, antibacterial, and pro-apoptotic activities. However, their role in mitochondrial function is still unclear. Our previous study showed that genes related to the mitochondria present significant changes in GA-treated mouse bone marrow stromal cells. We hypothesize that GAs may regulate mitochondrial function. Here, we found that GA treatment induced mitochondrial fragmentation, reduced mtDNA copy numbers and mitochondrial protein levels, and impaired mitochondrial adenosine 5'-triphosphate production and oxygen consumption. The GA-induced mitochondrial mass loss may be due to decreased mitochondrial biogenesis. In addition, abolishing autophagy by Atg7 knockout or the administration of an autophagy inhibitor can restore the GA-induced decrease in mitochondrial mass. Furthermore, FUNDC1 knockdown restored the GA-induced changes in mitochondrial mass reduction and mitochondrial membrane potential loss. Together, our studies demonstrated that GAs impaired mitochondrial function by decreasing mitochondrial biogenesis and promoting FUNDC1-dependent mitophagy.

Antiobesity Effect of Flaxseed Polysaccharide via Inducing Satiety due to Leptin Resistance Removal and Promoting Lipid Metabolism through the AMP-Activated Protein Kinase (AMPK) Signaling Pathway.

Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first induced to develop obesity by being fed a high-fat diet. The obese rats were then fed a control diet, AIN-93M (group HFD), or a 10% FP diet (group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, and serous proteins within the leptin-neuropeptide Y (NPY) and AMP-activated protein kinase (AMPK) signaling pathway were determined and analyzed. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15% ± 0.30% in group HFD to 478 ± 10 g and 1.38% ± 0.48% in group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.

Efficacy and mechanism of steep pulse irreversible electroporation technology on xenograft model of nude mice: a preclinical study.

BACKGROUND: Steep pulse therapy can irreversible electrically brackdown of tumor membrance and cause cell death. In previous studies, we investigated the effect of steep pulsed electroporation on the killing of large cell lung cancer cell line L981- in vitro, and determined the best parameters for killing lung cancer cells by steep pulse technology. But the optimal parameters and the mechanisms of steep pulse irreversible electroporation technology on nude mouse tumor model are unclear. METHODS: Three settings of steep pulse therapy parameters were applied to the nude mouse model. An in vivo imaging system was employed to observe the effect of different parameters on the mouse model. The pathological changes of the tumor tissue and immunofluorescence data on Caspase-3 protein expression were recorded. RESULTS: Under the in vivo imaging system, the steep pulse had an obvious inhibitory effect on the transplanted tumor in the nude mouse model. Pathological tests showed that occurrence of necrosis and apoptosis and expression of Caspase-3 protein in the tumor tissue were increased compared to those in the normal tissue. CONCLUSIONS: Steep pulse irreversible electroporation technology showed a promising antitumor effect in the nude mouse tumor model. With splint-type electrode, the best treatment parameters determined for the nude mouse tumor model were voltage amplitude 2000 V/cm, pulse width 100 µs, pulse frequency 1 Hz, pulse number 60, and repeat time 3. Moreover, steep pulse induced coagulative necrosis of tumor tissue by cell apoptosis.

Comprehensive Lipidome-Wide Profiling Reveals Dynamic Changes of Tea Lipids during Manufacturing Process of Black Tea.

As important biomolecules in Camellia sinensis L., lipids undergo substantial changes during black tea manufacture, which is considered to contribute to tea sensory quality. However, limited by analytical capacity, detailed lipid composition and its dynamic changes during black tea manufacture remain unclear. Herein, we performed tea lipidome profiling using high resolution liquid chromatography coupled to mass spectrometry (LC-MS), which allows simultaneous and robust analysis of 192 individual lipid species in black tea, covering 17 (sub)classes. Furthermore, dynamic changes of tea lipids during black tea manufacture were investigated. Significant alterations of lipid pattern were revealed, involved with chlorophyll degradation, metabolic pathways of glycoglycerolipids, and other extraplastidial membrane lipids. To our knowledge, this report presented most comprehensive coverage of lipid species in black tea. This study provides a global and in-depth metabolic map of tea lipidome during black tea manufacture.

[Interaction between microRNAs and OCT4].

Octamer-binding transcription factor 4 (OCT4) belongs to the POU-homeodomain family of transcription factors and binds to an octamer motif, ATGCAAAT. OCT4 is the key transcription factor that is involved in the maintenance of pluripotency and self-renewal in undifferentiated embryonic stem (ES) cells. OCT4 has been reported to be overexpressed in various cancers including lung, germ cell tumors, breast, cervix, prostate, gastric, liver, and ovarian cancer. MicroRNAs (miRNAs), small non-coding RNAs, modulate mRNA expression through base pairing between seed sequences in miRNA and complementary sequences of the target mRNA, thereby destabilizing mRNA and/or inhibiting protein synthesis. Several miRNAs have been demonstrated to regulate stemness factors such as OCT4, NANOG, SOX2 and KLF4 in cancer cells, thereby modulating the proliferation, apoptosis, differentiation, drug resistance and immunity of cancer cells.

Comparisons between the National Comprehensive Cancer Network (NCCN) non-small-cell lung cancer (NSCLC) Clinical Practice Guidelines (Chinese version), the NCCN original edition, and the European Society for Medical Oncology NSCLC Guidelines in 2009.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for various malignant tumors have been widely recognized and followed by global oncologists, in order to promote the standardization of cancer treatment and to provide the best treatment recommendations for cancer patients. However, there are still some differences in different countries and areas based on the specific conditions. In this paper, we compared the differences between NCCN non-small-cell lung cancer Clinical Practice Guidelines (Chinese version), the NCCN original edition, and European Society for Medical Oncology non-small-cell lung cancer guidelines.

Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer cell growth.

Elevated interleukin-6 (IL-6), a major mediator of the inflammatory response, has been implicated in androgen receptor (AR) activation, cellular growth and differentiation, plays important roles in the development and progression of prostate cancer, and is a potential target in cancer therapy. Through drug screening using human prostate cancer cells expressing IL-6 autocrine loop, we found that andrographolide, a diterpenoid lactone isolated from a traditional Chinese and Indian medicinal plant Andrographis paniculata, could inhibit IL-6 expression and suppress IL-6-mediated signals. Andrographolide inhibits IL-6 expression at both mRNA and protein levels in a dose-dependent manner. Andrographolide suppresses both IL-6 autocrine loop- and paracrine loop-induced cell signaling including Stat3 and Erk phosphorylation. Furthermore, andrographolide inhibits cell viability and induces apoptotic cell death in both androgen-stimulated and castration-resistant human prostate cancer cells without causing significant toxicity to normal immortalized prostate epithelial cells. Moreover, treatment of andrographolide to mice bearing castration-resistant DU145 human prostate tumors that express constitutive IL-6 autocrine loop significantly suppresses tumor growth. Taken together, these results demonstrate that andrographolide could be developed as a therapeutic agent to treat both androgen-stimulated and castration-resistant prostate cancer possibly by suppressing IL-6 expression and IL-6-induced signaling.

[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus].

BACKGROUND & OBJECTIVE: H101 is an E1B-55 kDa gene-deleted replication-selective adenovirus, which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combined with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluorouracil (AF) regimen versus PF or AF regimen alone in treating patients with head and neck or esophagus squamous cell cancer. METHODS: A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m(2) ivgtt, qd x 5d; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients have no history of PF chemotherapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m(2) iv,d1; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients didn't response to PF regimen. All patients were randomized to either receive intratumoral H101 injection (5.0 x 10(11)-1.5 x 10(12) VP/day for 5 consecutive days every 3 weeks) or not. Treatment repeated every 3 weeks,all patients have to receive at least 2 cycles of chemotherapy. RESULTS: Among 123 accordant patients,overall response rate of PF plus H101 group (group A1) was 78.8% (41/52),of PF alone group (group B1) was 39.6% (21/53),of AF plus H101 group (group A2) was 50.0% (7/14),of AF alone group (group B2) was 50.0% (2/4). Differences of response rates between group A1 and group B1,between group A1+A2 and group B1+B2 were significant (P=0.000). Main side effects were fever (45.7%), injection site reaction (28.3%),and influenza-like symptoms (9.8%). CONCLUSION: Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.

[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].

BACKGROUND & OBJECTIVE: In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer. METHODS: A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded. RESULTS: Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P< 0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients. CONCLUSION: The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.

[Monitoring of the renal function changes during chemotherapy based on high-dose cisplatin in patients with lung cancer].

BACKGROUND: To study the methods for monitoring nephrotoxicity of cisplatin in lung cancer chemotherapy. METHODS: The serum urea nitrogen (BUN), creatine (Cr) and urine ß2-microglobulin ( ß2-MG),α1-microglobulin(α1-MG), albumin (Alb), transferrin (TRF), and retinol-binding-protein (RBP) were measured dynamically in 61 patients with lung cancer who received high-dose chemotherapy with DDP (80- 120 mg/m2) (totally 114 cycles), and some indexes of early nephrotxcity were screened. RESULTS: At the early stage of chemotherapy (d1-5), the abnormal rates of urine ß2-MG and α1-MG were much more predominant than those of other indexes (P < 0.001). The abnormal rates of serum BUN and Cr were increased significantly in the late period of chemotherapy (d10). There were abnormal elevation of urine ß2-MG and/or α1-MG at the early stage of chemotherapy for the patients whose serum BUN and creatine were all abnormal at the late stage. CONCLUSIONS: The urine ß2-MG and /or α1-MG might be the valuable indexes for early diagnosis of nephrotoxicity in lung cancer chemotherapy with cisplatin.