Lung cancer is the leading cause of cancer-related deaths worldwide， and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition （EMT） is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated， polarized， and organized epithelial cells， which acquire motility， migratory potential， and invasive properties. During this process， cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype， accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors， post-translational controls， epigenetic modifications， and non-coding RNAs. Therefore， therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years， EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine， with its characteristics of multi-target action， low side effects， and good therapeutic efficacy， has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine， including flavonoids， glycosides， phenols， terpenoids， saccharides， and alkaloids， as well as Chinese medicine compound formulas， have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways， targets， and links， including signaling pathways， exosomes， microRNAs （miRNAs）， and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients， monomers， and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

OBJECTIVES: To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE). METHODS: Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted. RESULTS: Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies. CONCLUSIONS Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.
Animals ; Female ; MicroRNAs/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endometrium/pathology* ; Rats, Sprague-Dawley ; Rats ; Moxibustion ; Pyroptosis ; Up-Regulation ; Interleukin-1beta/metabolism* ; Interleukin-18 ; Caspase 1/metabolism*

Objective To analyze the global burden of disease and cross-national imbalances of tracheal,bronchial and lung cancer from 1990-2021 and to further predict changes up to 2040.Methods Age-standardised incidence rate(ASIR),prevalence rate(ASPR),mortality rate(ASMR),disability-adjusted life years rate(ASDR)and 95%confidence interval(95%UI)were extracted from GHDx.The official data platform of the institute for health metrics and evaluation(IHME)and the source of data were the Global Burden of Disease Study 2021(GBD 2021)for global burden of disease of trachea,bronchus and lung cancer.The estimated annual percentage change(EAPC)was calculated to describe the prevalence at global,regional and national levels,to understand the differences in diseases at different gender,age and socio-demographic index(SDI)levels,and to explore the overall situation through cluster analysis,cross-country health inequality analysis and to predict the future prevalence up to 2040 through Nordpred model.Results Globally,the ASIR for tracheal,bronchial and lung cancer fluctuated slightly from 1990 to 2009,and began to decline rapidly after 2009,with an ASIR of 26.42/100 000 in 2021.ASPR showed an increasing and then decreasing trend,reaching a peak in 2011,with a peak of 37.28/100 000 in 2021,while the ASMR and the ASDR showed a general decreasing trend.Tracheal,bronchial and lung cancer diseases showed the highest disease burden in men,those aged 65-74 and in countries and regions with high SDI.ASDR burden showed significant inequalities globally,with a significant positive correlation between ASDR and SDI,mainly concentrated in countries and regions with high SDI,and the unequal burden of ASDR for tracheal,bronchial and lung cancer decreases over time.Predictive analyses found that the number of new cases,current cases,deaths and disability-adjusted life years(DALY)for tracheal,bronchial and lung cancer were expected to increase through 2040,whereas ASIR,ASPR,ASMR and ASDR were projected to decrease each year.Conclusion The overall burden of tracheal,bronchial and lung cancer has declined globally from 1990 to 2021,but with demographic and regional differences.The actual number of cases will continue to climb in the future,despite the continuing decline in age-specified rates,and disease prevention and control will need to focus on growth trends and equity in resource allocation.

Objective To analyze the global burden of disease and cross-national imbalances of tracheal,bronchial and lung cancer from 1990-2021 and to further predict changes up to 2040.Methods Age-standardised incidence rate(ASIR),prevalence rate(ASPR),mortality rate(ASMR),disability-adjusted life years rate(ASDR)and 95%confidence interval(95%UI)were extracted from GHDx.The official data platform of the institute for health metrics and evaluation(IHME)and the source of data were the Global Burden of Disease Study 2021(GBD 2021)for global burden of disease of trachea,bronchus and lung cancer.The estimated annual percentage change(EAPC)was calculated to describe the prevalence at global,regional and national levels,to understand the differences in diseases at different gender,age and socio-demographic index(SDI)levels,and to explore the overall situation through cluster analysis,cross-country health inequality analysis and to predict the future prevalence up to 2040 through Nordpred model.Results Globally,the ASIR for tracheal,bronchial and lung cancer fluctuated slightly from 1990 to 2009,and began to decline rapidly after 2009,with an ASIR of 26.42/100 000 in 2021.ASPR showed an increasing and then decreasing trend,reaching a peak in 2011,with a peak of 37.28/100 000 in 2021,while the ASMR and the ASDR showed a general decreasing trend.Tracheal,bronchial and lung cancer diseases showed the highest disease burden in men,those aged 65-74 and in countries and regions with high SDI.ASDR burden showed significant inequalities globally,with a significant positive correlation between ASDR and SDI,mainly concentrated in countries and regions with high SDI,and the unequal burden of ASDR for tracheal,bronchial and lung cancer decreases over time.Predictive analyses found that the number of new cases,current cases,deaths and disability-adjusted life years(DALY)for tracheal,bronchial and lung cancer were expected to increase through 2040,whereas ASIR,ASPR,ASMR and ASDR were projected to decrease each year.Conclusion The overall burden of tracheal,bronchial and lung cancer has declined globally from 1990 to 2021,but with demographic and regional differences.The actual number of cases will continue to climb in the future,despite the continuing decline in age-specified rates,and disease prevention and control will need to focus on growth trends and equity in resource allocation.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Bone diseases, such as osteoporosis and osteoarthritis, have emerged as pressing public health concerns requiring immediate attention and resolution. Cellular therapy and tissue engineering techniques are among the most promising therapeutic approaches for such conditions. Human induced pluripotent stem cells (hiPSCs) possess remarkable capacity for indefinite self-renewal in vitro and the ability to differentiate into all somatic cell types originating from the three germ layers, thereby making them a promising source of osteoblasts. Consequently, it is crucial to establish a well-delineated system for osteogenic differentiation of hiPSCs in vitro, with the aim to generate osteoblast-like cells that conform to clinical application standards. Numerous research teams have achieved substantial advancements in both the direct osteogenic differentiation of hiPSCs and the indirect pathway via mesenchymal stem cells. In this article, we provide a comprehensive review of these two osteogenic differentiation pathways and their current applications, with the aim of serving as a valuable reference for bone regeneration technologies. Current research efforts have relied on embryoid body formation and monolayer induction methods utilizing biomaterials to develop a system that facilitates in vitro culture and osteogenic differentiation of hiPSCs. However, the existing research is primarily constrained by unclear system components and low efficiency. Therefore, the development of a stepwise and three-dimensional induction system based on stringent regulation by specific compounds is a primary research direction for the future.

BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Purpose: To identify the predictors of infectious disease-specific health literacy (IDSHL), and establish an easy-to-apply nomogram to predict the IDSHL of older adults. Methods: This cross-sectional study included 380 older adults who completed the IDSHL, self-rated health, socio-demographic and other questionnaires. Logistic regression was used to identify the IDSHL predictors. Nomogram was used to construct a predictive model. Results: Up to 70.1% of older adults had limited IDSHL. Age, education, place of residence, self-rated health, and Internet access were the important influencing factors of IDSHL. The established nomogram model showed high accuracy (receiver operating characteristic curve: 0.848). Conclusions The IDSHL of Chinese older adults was significantly deficient. The constructed nomogram is an intuitive tool for IDSHL prediction that can not only contribute toward rapid screening of high-risk older adults with limited IDSHL but also provide guidance for healthcare providers to develop prevention strategies for infectious diseases.