Single-cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation.

BACKGROUND: Aberrant activation of the phosphatidlinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway has been shown to play an important role in lung adenocarcinoma (LUAD). The effect of KRAS mutations, one of the important signatures of LUAD, on the PI3K/AKT/mTOR pathway in LUAD remains unclear. METHODS: The Seurat package and principal component analysis were used for cell categorization of single-cell RNA sequencing data of LUAD. The AUCell score was used to assess the activity of the PI3K/AKT/mTOR pathway. Meanwhile, using the gene expression profiles and mutation profiles in the The Cancer Genome Atlas dataset, LUAD patients were categorized into KRAS-mutant (KRAS-MT) and KRAS-wild-types (KRAS-WT), and the corresponding enrichment scores were calculated using gene set enrichment analysis analysis. Finally, the subpopulation of cells with the highest pathway activity was identified, the copy number variation profile of this subpopulation was inscribed using the inferCNV package and the CMap database was utilized to make predictions for drugs targeting this subpopulation. RESULTS: There is higher PI3K/AKT/mTOR pathway activity in LUAD epithelial cells with KRAS mutations, and high expression of KRAS, PIK3CA, AKT1 and PDPK1. In particular, we found significantly higher levels of pathway activity and associated gene expression in KRAS-MT than in KRAS-WT. We identified the highest pathway activity on a subpopulation of GRB2+ epithelial cells and the presence of amplified genes within its pathway. Finally, drugs were able to target GRB2+ epithelial cell subpopulations, such as wortmannin, palbociclib and angiogenesis inhibitor. CONCLUSIONS: The present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.

Overview and Comparison of Chinese and Western Medical Treatments for Osteoporosis.

Objective: Traditional Chinese medicine (TCM) can achieve similar effects to Western medicine in increasing bone mineral density, improving the destruction of bone micro-structure, inhibiting bone resorption, etc. However, there exist great differences between TCM and Western medicine in terms of theoretical basis and treatment methods. Therefore, to gain insights into their differences in treating osteoporosis (OP), we compared the disease name, etiology, pathogenesis, and clinical effectiveness to explore the potential benefits of combining the two approaches. Methods Overview: The method of literature review is used in the study. We firstly use academic databases such as PubMed and CNKI to search relevant literature on the understanding of OP in TCM and Western medicine in the past 10 years, then exclude the literature that is not relevant to the study topic or does not meet the study purpose, and finally compare and summarize the findings, views and conclusions of the literature. Key Findings or Insights: In the study, we find that the integrated approach of TCM and Western medicine can provide a gentler and more individualized treatment for patients with OP. By combining the conditioning means of Chinese herbs, compound prescription, acupuncture, moxibustion and Tuina can make up for the adverse reactions and side effects of Western medicine. Besides, TCM can make use of the clinical trials and animal experiments of Western medicine to prove the effectiveness of TCM theories and promote the clinical application. Practical Implications: By exploring the differences between TCM and Western medicine and the potential benefits of their combination, this study can provide a theoretical basis for the individualized treatment of OP. Especially for the patients with postmenopausal OP, senile OP, long-term hormone use, hyperthyroidism and other secondary OP, this study can provide a more comprehensive rehabilitation guidance, prevent the recurrence of these diseases, and improve the quality of patients' life. Recommendations or Future Directions: It is suggested that further clinical trials should be conducted to evaluate the effectiveness of the integrated treatment.

Attitudes and influencing factors associated with smoking cessation: An online cross-sectional survey in China.

INTRODUCTION: Quitting smoking, the critical path to reach the global targets of reducing tobacco use, can bring major and immediate health benefits to smokers. Exploring factors that help individuals to quit smoking is of great importance. The present study explored influencing factors on smoking cessation, in order to provide comprehensive reference for tobacco control policies. METHODS: Ex-smokers and current smokers were recruited online in this cross-sectional survey, from 1 October to 31 November 2022, in China. The observational data were collected using a questionnaire to collect information with respect to sociodemographic characteristics of smokers, attitudes towards smoking cessation, details of smoking cessation, and different potential factors related to smoking cessation through open-ended questions. RESULTS: A total of 638 smokers from 30 provinces were recruited as eligible respondents, with a mean age of 37.3 ± 11.7 years and a mean smoking history of 15.9 ± 13.7 years. The percentage of males was 92.3%. Of the 638 respondents, only 3.9% had no intention to stop smoking. Among 155 subjects who had quitted smoking successfully, willpower (55.5%) was considered as the most important contributing factor. Among 365 subjects who tried to quit but failed, lack of willpower (28.2%), tobacco dependence (16.2%), influence of surrounding smokers or smoking environments (15.9%), bad moods (9.9%), stress from work or life (7.9%), habits (7.1%), socialization (4.1%), and easy availability of tobacco (2.7%) were considered as the adverse factors leading to failure in quitting smoking. CONCLUSIONS: Willpower and support from family members were the vital factors that lead to successful smoking cessation. Future tobacco control policies should also focus on addressing withdrawal symptoms and creating smoke-free environments as well as other factors.

Seven compounds from Portulaca oleracea L. and their anticholinesterase activities.

A novel lignan, identified as 4-(3,4-dihydroxyphenyl)-6,7-dimethoxy-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one, named oleralignan A (1), together with six known compounds, loliolide (2), isololiolide (3), dehydrololiolide (4), daphnetin (5), esculetin (6), and trans-coumaric acid methyl ester (7) was obtained from Portulaca oleracea L., while compounds 3, 4, 6, and 7 were isolated from the plant for the first time. Their structures were elucidated using spectroscopic methods, including one- and two-dimensional NMR and high-resolution electrospray ionization time-of-flight mass spectrometry. In addition, the results of activity assay demonstrated that compounds 1-7 have anticholinesterase activities.

Two new organic acids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities.

Two new organic acids, identified as (7E,9E,12E)-pentadecyl-7,9,12-trienoic acid, named Oleraceacid A (1), and 6,7-dihydroxy-4-(4-hydroxy-3,5-dimethoxyphenyl)-2-naphthoic acid, named Oleraceacid B (2), were isolated from Portulaca oleracea L.. The structures were verified by spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1 D and 2 D NMR. Both Oleraceacid A (1) and Oleraceacid B (2) at 20 µM inhibited the inflammatory factor, IL-1ß in the RAW 264.7 cells induced by LPS, moreover, Oleraceacid A (1) can inhibit cholinesterase activity.

[First discrimination of the meanings of the seven words relevant with acupuncture in Huangdi Nei- jing (Yellow Emnerors Internal Classic)].

Huangdi Neijing (Yellow Emperor's Internal Classic) is the earliest medical classic work existing at present in Chinese medical treasures and is the foundation of TCM. It not only contains rich medical words, but also supplements the new meanings of seven words, i. e. Wang, Xiu, Yuan, Fang, Xu, Jiu and Bian for removing needle, retaining needling, reinforcing technique, reducing technique, slow needling, moxibustion and stone-needle puncturing, respectively.